Journal articles on the topic 'Protein expression; Fusobacterium nucleatum; biofilm'
To see the other types of publications on this topic, follow the link: Protein expression; Fusobacterium nucleatum; biofilm.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Protein expression; Fusobacterium nucleatum; biofilm.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Schnurr, Etyene, Pune N. Paqué, Thomas Attin, Paolo Nanni, Jonas Grossmann, Silva Holtfreter, Barbara M. Bröker, et al. "Staphylococcus aureus Interferes with Streptococci Spatial Distribution and with Protein Expression of Species within a Polymicrobial Oral Biofilm." Antibiotics 10, no. 2 (January 26, 2021): 116. http://dx.doi.org/10.3390/antibiotics10020116.
Full textAbstract:
We asked whether transient Staphylococcus aureus in the oral environment synergistically interacts with orally associated bacterial species such as Actinomyces oris, Candida albicans, Fusobacterium nucleatum, Streptococcus oralis, Streptococcus mutans, and Veillonella dispar (six-species control biofilm 6S). For this purpose, four modified biofilms with seven species that contain either the wild type strain of the S. aureus genotype (USA300-MRSA WT), its isogenic mutant with MSCRAMM deficiency (USA300-MRSA ΔMSCRAMM), a methicillin-sensitive S. aureus (ST72-MSSA-) or a methicillin-resistant S. aureus (USA800-MRSA) grown on hydroxyapatite disks were examined. Culture analyses, confocal-laser-scanning microscopy and proteome analyses were performed. S. aureus strains affected the amount of supragingival biofilm-associated species differently. The deletion of MSCRAMM genes disrupted the growth of S. aureus and the distribution of S. mutans and S. oralis within the biofilms. In addition, S. aureus caused shifts in the number of detectable proteins of other species in the 6S biofilm. S. aureus (USA300-MRSA WT), aggregated together with early colonizers such as Actinomyces and streptococci, influenced the number of secondary colonizers such as Fusobacterium nucleatum and was involved in structuring the biofilm architecture that triggered the change from a homeostatic biofilm to a dysbiotic biofilm to the development of oral diseases.
2
Sasaki-Imamura, Takako, Akira Yano, and Yasuo Yoshida. "Production of Indole from l-Tryptophan and Effects of These Compounds on Biofilm Formation by Fusobacterium nucleatum ATCC 25586." Applied and Environmental Microbiology 76, no. 13 (May 14, 2010): 4260–68. http://dx.doi.org/10.1128/aem.00166-10.
Full textAbstract:
ABSTRACT The l-tryptophan degradation product indole is a purported extracellular signaling molecule that influences biofilm formation in various bacteria. Here we analyzed the mechanisms of indole production in Fusobacterium nucleatum and the effects of tryptophan and indole on F. nucleatum planktonic and biofilm cells. The amino acid sequence deduced from the fn1943 gene in F. nucleatum ATCC 25586 was 28% identical to that deduced from tnaA in Escherichia coli, which encodes tryptophanase catalyzing the β-elimination of l-tryptophan to produce indole. The fn1943 gene was cotranscribed with the downstream gene fn1944, which is a homolog of tnaB encoding low-affinity tryptophan permease. The transcript started at position −68 or −153 from the first nucleotide of the fn1943 translation initiation codon. Real-time quantitative PCR showed that much more F. nucleatum fn1943 transcripts were obtained from log-phase cells than from stationary-phase cells. Indole production by the purified recombinant protein encoded by fn1943 was examined using high-performance liquid chromatography. The Km and k cat of the enzyme were 0.26 ± 0.03 mM and 0.74 ± 0.04 s−1, respectively. F. nucleatum biofilm formation and the biofilm supernatant concentration of indole increased dose dependently with increasing tryptophan concentrations. Exogenous indole also increased F. nucleatum biofilm formation in a dose-dependent manner. Even at very high concentrations, tryptophan did not affect fn1943 expression, whereas similar indole concentrations decreased expression. Thus, exogenous tryptophan and indole were suggested to increase F. nucleatum biofilms.
3
Honma, Kiyonobu, Elina Mishima, Satoru Inagaki, and Ashu Sharma. "The OxyR homologue in Tannerella forsythia regulates expression of oxidative stress responses and biofilm formation." Microbiology 155, no. 6 (June 1, 2009): 1912–22. http://dx.doi.org/10.1099/mic.0.027920-0.
Full textAbstract:
Tannerella forsythia is an anaerobic periodontal pathogen that encounters constant oxidative stress in the human oral cavity due to exposure to air and reactive oxidative species from coexisting dental plaque bacteria as well as leukocytes. In this study, we sought to characterize a T. forsythia ORF with close similarity to bacterial oxidative stress response sensor protein OxyR. To analyse the role of this OxyR homologue, a gene deletion mutant was constructed and characterized. Aerotolerance, survival after hydrogen peroxide challenge and transcription levels of known bacterial antioxidant genes were then determined. Since an association between oxidative stress and biofilm formation has been observed in bacterial systems, we also investigated the role of the OxyR protein in biofilm development by T. forsythia. Our results showed that aerotolerance, sensitivity to peroxide challenge and the expression of oxidative stress response genes were significantly reduced in the mutant as compared with the wild-type strain. Moreover, the results of biofilm analyses showed that, as compared with the wild-type strain, the oxyR mutant showed significantly less autoaggregation and a reduced ability to form mixed biofilms with Fusobacterium nucleatum. In conclusion, a gene annotated in the T. forsythia genome as an oxyR homologue was characterized. Our studies showed that the oxyR homologue in T. forsythia constitutively activates antioxidant genes involved in resistance to peroxides as well as oxygen stress (aerotolerance). In addition, the oxyR deletion attenuates biofilm formation in T. forsythia.
4
Fong, Karen P., Whasun O. Chung, Richard J. Lamont, and Donald R. Demuth. "Intra- and Interspecies Regulation of Gene Expression by Actinobacillus actinomycetemcomitansLuxS." Infection and Immunity 69, no. 12 (December 1, 2001): 7625–34. http://dx.doi.org/10.1128/iai.69.12.7625-7634.2001.
Full textAbstract:
ABSTRACT The cell density-dependent control of gene expression is employed by many bacteria for regulating a variety of physiological functions, including the generation of bioluminescence, sporulation, formation of biofilms, and the expression of virulence factors. Although periodontal organisms do not appear to secrete acyl-homoserine lactone signals, several species, e.g., Porphyromonas gingivalis,Prevotella intermedia, and Fusobacterium nucleatum, have recently been shown to secrete a signal related to the autoinducer II (AI-2) of the signal system 2 pathway inVibrio harveyi. Here, we report that the periodontal pathogen Actinobacillus actinomycetemcomitans expresses a homolog of V. harveyi luxS and secretes an AI-2-like signal. Cell-free conditioned medium from A. actinomycetemcomitans or from a recombinant Escherichia coli strain (E. coli AIS) expressing A. actinomycetemcomitans luxS induced luminescence in V. harveyi BB170 >200-fold over controls. AI-2 levels peaked in mid-exponential-phase cultures of A. actinomycetemcomitans and were significantly reduced in late-log- and stationary-phase cultures. Incubation of early-log-phaseA. actinomycetemcomitans cells with conditioned medium from A. actinomycetemcomitans or from E. coli AIS resulted in a threefold induction of leukotoxic activity and a concomitant increase in leukotoxin polypeptide. In contrast, no increase in leukotoxin expression occurred when cells were exposed to sterile medium or to conditioned broth from E. coli AIS−, a recombinant strain in whichluxS was insertionally inactivated. A. actinomycetemcomitans AI-2 also induced expression ofafuA, encoding a periplasmic iron transport protein, approximately eightfold, suggesting that LuxS-dependent signaling may play a role in the regulation of iron acquisition by A. actinomycetemcomitans. Finally, A. actinomycetemcomitans AI-2 added in transcomplemented a luxS knockout mutation in P. gingivalis by modulating the expression of theluxS-regulated genes uvrB andhasF in this organism. Together, these results suggest that LuxS-dependent signaling may modulate aspects of virulence and the uptake of iron by A. actinomycetemcomitans and induce responses in other periodontal organisms in mixed-species oral biofilm.
5
Bachtiar, Endang W., Boy M. Bachtiar, Ardiana Kusumaningrum, Hari Sunarto, Yuniarti Soeroso, Benso Sulijaya, Efa Apriyanti, et al. "ACE2 expression in saliva of patients with COVID-19 and its association with Candida albicans and Aggregatibacter actinomycetemcomitans." F1000Research 11 (May 23, 2022): 557. http://dx.doi.org/10.12688/f1000research.111965.1.
Full textAbstract:
Background: A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora and expression of angiotensin-converting enzyme 2 (ACE2) remains to be established. In this observational study, we collected saliva from patients with COVID-19 and evaluated the relationship between ACE2 expression and Candida albicans as well as with selected gram-negative bacteria (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Veillonella parvula). We investigated how this may be directly or indirectly involved in oral dysbiosis in patients with COVID-19. Methods: We included 23 hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, with six healthy participants serving as controls. Saliva and tongue surface swabs were collected from patients with diabetes (DG) and without diabetes (NDG) and subject controls. Using quantitative PCR (qPCR) we assessed the mRNA expression of ACE2, the abundance of C. albicans, and the transcription levels of its biofilm-associated genes, agglutinin-like protein 3 (ALS3), hyphal wall protein 1 (HWP1), and yeast-form wall protein 1 (YWP1). We also counted the relative proportion of the three selected gram-negative oral bacteria in saliva. All analyses were performed to determine the relationship between ACE2 expression and C. albicans and gram-negative bacteria. Results: ACE2 mRNA expression was significantly higher in tongue swab samples than in saliva. However, no significant difference was observed between the patient groups. Conversely, DG patients had a significantly higher abundance of C. albicans in saliva compared to NDG patients and control group patients. The correlation and sensitivity/specificity relationship between ACE2 expression and C. albicans or the selected oral bacteria were also observed. Conclusions: The data show that ACE2 expression can be detected in saliva of patients with COVID-19 and its association with C. albicans and gram-negative oral bacteria might contribute toward developing an oral dysbiosis based predictor for prognosis of COVID-19 severity.
6
Bachtiar, Endang W., Boy M. Bachtiar, Ardiana Kusumaningrum, Hari Sunarto, Yuniarti Soeroso, Benso Sulijaya, Efa Apriyanti, et al. "ACE2 expression in saliva of patients with COVID-19 and its association with Candida albicans and Aggregatibacter actinomycetemcomitans." F1000Research 11 (September 12, 2022): 557. http://dx.doi.org/10.12688/f1000research.111965.2.
Full textAbstract:
Background: A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora and expression of angiotensin-converting enzyme 2 (ACE2) remains to be established. In this observational study, we collected saliva from patients with COVID-19 and evaluated the relationship between ACE2 expression and Candida albicans as well as with selected gram-negative bacteria (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Veillonella parvula). We investigated how this may be directly or indirectly involved in oral dysbiosis in patients with COVID-19. Methods: We included 23 hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, with six healthy participants serving as controls. Saliva and tongue surface swabs were collected from patients with diabetes (DG) and without diabetes (NDG) and subject controls. Using quantitative PCR (qPCR) we assessed the mRNA expression of ACE2, the abundance of C. albicans, and the transcription levels of its biofilm-associated genes, agglutinin-like protein 3 (ALS3), hyphal wall protein 1 (HWP1), and yeast-form wall protein 1 (YWP1). We also counted the relative proportion of the three selected gram-negative oral bacteria in saliva. All analyses were performed to determine the relationship between ACE2 expression and C. albicans and gram-negative bacteria. Results: ACE2 mRNA expression was significantly higher in tongue swab samples than in saliva. However, no significant difference was observed between the patient groups. Conversely, DG patients had a significantly higher abundance of C. albicans in saliva compared to NDG patients and control group patients. The correlation and sensitivity/specificity relationship between ACE2 expression and C. albicans or the selected oral bacteria were also observed. Conclusions: The data show that ACE2 expression can be detected in saliva of patients with COVID-19 and its association with C. albicans and gram-negative oral bacteria might contribute toward developing an oral dysbiosis based predictor for prognosis of COVID-19 severity.
7
Kaplan, C. W., R. Lux, T. Huynh, A. Jewett, W. Shi, and S. Kinder Haake. "Fusobacterium nucleatum Apoptosis-inducing Outer Membrane Protein." Journal of Dental Research 84, no. 8 (August 2005): 700–704. http://dx.doi.org/10.1177/154405910508400803.
Full textAbstract:
The periodontal pathogen Fusobacterium nucleatum induces apoptosis in lymphocytes. We previously identified the autotransporter protein Fap2 in F. nucleatum strain PK1594 that induced apoptosis in lymphocytes when expressed in Escherichia coli. In this study, we identified protein homologs of Fap2 in the transformable F. nucleatum strain ATCC 23726, to determine their role in the induction of apoptosis in lymphocytes. We used a new gene-inactivation vector conferring thiamphenicol resistance (pHS31) to construct a mutant deficient in one of the homologs, aim1. Transcriptional analyses demonstrated disruption of aim1 expression, and phenotypic analyses revealed a 41% decrease in the ability of the mutant to induce apoptosis in Jurkat cells, as compared with the parental strain. These studies demonstrate, in the native host cell background, the contribution of aim1 to F. nucleatum induction of apoptosis and, to the best of our knowledge, represent the first report of a genetically defined and phenotypically characterized mutation in F. nucleatum.
8
Mendes, Reila Tainá, Daniel Nguyen, Danielle Stephens, Ferda Pamuk, Daniel Fernandes, Thomas E. Van Dyke, and Alpdogan Kantarci. "Endothelial Cell Response to Fusobacterium nucleatum." Infection and Immunity 84, no. 7 (May 16, 2016): 2141–48. http://dx.doi.org/10.1128/iai.01305-15.
Full textAbstract:
Vascular response is an essential aspect of an effective immune response to periodontal disease pathogens, as new blood vessel formation contributes to wound healing and inflammation. Gaining a greater understanding of the factors that affect vascular response may then contribute to future breakthroughs in dental medicine. In this study, we have characterized the endothelial cell response to the common bacteriumFusobacterium nucleatum, an important bridging species that facilitates the activity of late colonizers of the dental biofilm. Endothelial cells were infected withFusobacterium nucleatum(strain 25586) for periods of 4, 12, 24, or 48 h. Cell proliferation and tube formation were analyzed, and expression of adhesion molecules (CD31 and CD34) and vascular endothelial growth factor (VEGF) receptors 1 and 2 was measured by fluorescence-activated cell sorter (FACS) analysis. Data indicate thatF. nucleatumimpaired endothelial cell proliferation and tube formation. The findings suggest that the modified endothelial cell response acts as a mechanism promoting the pathogenic progression of periodontal diseases and may potentially suggest the involvement of periodontopathogens in systemic diseases associated with periodontal inflammation.
9
Uitto, Veli-Jukka, Daniel Baillie, Qiang Wu, Renee Gendron, Daniel Grenier, Edward E. Putnins, Arja Kanervo, and James D. Firth. "Fusobacterium nucleatum Increases Collagenase 3 Production and Migration of Epithelial Cells." Infection and Immunity 73, no. 2 (February 2005): 1171–79. http://dx.doi.org/10.1128/iai.73.2.1171-1179.2005.
Full textAbstract:
ABSTRACT Fusobacterium nucleatum is closely associated with human periodontal diseases and may also be a causative agent in other infections, such as pericarditis, septic arthritis, and abscesses of tonsils and liver. Initiation and outcome of infective diseases depend critically on the host cell signaling system altered by the microbe. Production of proteinases by infected cells is an important factor in pericellular tissue destruction and cell migration. We studied binding of F. nucleatum to human epithelial cells (HaCaT keratinocyte line) and subsequent cell signaling related to collagenase 3 expression, cell motility, and cell survival, using a scratch wound cell culture model. F. nucleatum increased levels of 12 protein kinases involved in cell migration, proliferation, and cell survival signaling, as assessed by the Kinetworks immunoblotting system. Epithelial cells of the artificial wound margins were clearly preferential targets of F. nucleatum. The bacterium colocalized with lysosomal structures and stimulated migration of these cells. Of the 13 anaerobic oral bacterial species, F. nucleatum and Fusobacterium necrophorum were among the best inducers of collagenase 3 mRNA levels, a powerful matrix metalloproteinase. Production of collagenase 3 was detected in fusobacterium-infected cells and cell culture medium by immunocytochemistry, immunoblotting, and zymography. The proteinase production involved activation of p38 mitogen-activated protein kinase in the infected cells. The study suggests that F. nucleatum may be involved in the pathogenesis of periodontal diseases (and other infections) by activating multiple cell signaling systems that lead to stimulation of collagenase 3 expression and increased migration and survival of the infected epithelial cells.
10
Bachrach, Gilad, Susan Kinder Haake, Alon Glick, Ronen Hazan, Ronit Naor, Roxanna N. Andersen, and Paul E. Kolenbrander. "Characterization of the Novel Fusobacterium nucleatum Plasmid pKH9 and Evidence of an Addiction System." Applied and Environmental Microbiology 70, no. 12 (December 2004): 6957–62. http://dx.doi.org/10.1128/aem.70.12.6957-6962.2004.
Full textAbstract:
ABSTRACT Fusobacterium nucleatum is an important oral anaerobic pathogen involved in periodontal and systemic infections. Studies of the molecular mechanisms involved in fusobacterial virulence and adhesion have been limited by lack of systems for efficient genetic manipulation. Plasmids were isolated from eight strains of F. nucleatum. The smallest plasmid, pKH9 (4,975 bp), was characterized and used to create new vectors for fusobacterial genetic manipulation. DNA sequence analysis of pKH9 revealed an open reading frame (ORF) encoding a putative autonomous rolling circle replication protein (Rep), an ORF predicted to encode a protein homologous to members of the FtsK/SpoIIIE cell division-DNA segregation protein family, and an operon encoding a putative toxin-antitoxin plasmid addiction system (txf-axf). Deletion analysis localized the pKH9 replication region in a 0.96-kbp fragment. The pKH9 rep gene is not present in this fragment, suggesting that pKH9 can replicate in fusobacteria independently of the Rep protein. A pKH9-based, compact Escherichia coli-F. nucleatum shuttle plasmid was constructed and found to be compatible with a previously described pFN1-based fusobacterial shuttle plasmid. Deletion of the pKH9 putative addiction system (txf-axf) reduced plasmid stability in fusobacteria, indicating its addiction properties and suggesting it to be the first plasmid addiction system described for fusobacteria. pKH9, its genetic elements, and its shuttle plasmid derivatives can serve as useful tools for investigating fusobacterial properties important in biofilm ecology and pathogenesis.
11
Lee, Seok-Joo, and Bong-Kyu Choi. "Involvement of NLRP10 in IL-1α induction of oral epithelial cells by periodontal pathogens." Innate Immunity 23, no. 7 (August 2, 2017): 569–77. http://dx.doi.org/10.1177/1753425917722610.
Full textAbstract:
This study investigated the pathogenesis of periodontitis and the role of nucleotide-binding oligomerization domain-like receptor protein 10 (NLRP10). The human oral epithelial cell line HOK-16B was infected with two periodontal pathogens, Tannerella forsythia and Fusobacterium nucleatum, at various MOIs. RT-PCR and immunoblotting demonstrated that infection increased mRNA and protein expression of NLRP10, respectively. The siRNA-mediated NLRP10 knockdown significantly reduced IL-1α expression and secretion. Both bacteria induced phosphorylation of ERK, JNK and p38 MAP kinases in HOK-16B cells. NLRP10 knockdown impaired ERK phosphorylation only. ERK inhibition significantly decreased the expression of T. forsythia- and F. nucleatum-induced IL-1α. Our data suggest that NLRP10 is involved in activating the ERK signalling pathway in HOK-16B cells infected with T. forsythia and F. nucleatum. This pathway likely augments the pro-inflammatory cytokine IL-1α levels, which may play a critical role in periodontitis.
12
Zhao, Tian, Jiaqi Chen, Shuai Liu, Jie Yang, Juan Wu, Leiying Miao, and Weibin Sun. "Transcriptome analysis of Fusobacterium nucleatum reveals differential gene expression patterns in the biofilm versus planktonic cells." Biochemical and Biophysical Research Communications 593 (February 2022): 151–57. http://dx.doi.org/10.1016/j.bbrc.2021.11.075.
Full text
13
Zhou, Ting, Xianhong Meng, Daxiu Wang, Weiran Fu, and Xinrui Li. "Neutrophil Transcriptional Deregulation by the Periodontal Pathogen Fusobacterium nucleatum in Gastric Cancer: A Bioinformatic Study." Disease Markers 2022 (August 18, 2022): 1–10. http://dx.doi.org/10.1155/2022/9584507.
Full textAbstract:
Background. Infection with the periodontal pathogen Fusobacterium nucleatum (F. nucleatum) has been associated with gastric cancer. The present study is aimed at uncovering the putative biological mechanisms underlying effects of F. nucleatum–mediated neutrophil transcriptional deregulation in gastric cancer. Materials and Methods. A gene expression dataset pertaining to F. nucleatum-infected human neutrophils was utilized to identify differentially expressed genes (DEGs) using the GEO2R tool. Candidate genes associated with gastric cancer were sourced from the “Candidate Cancer Gene Database” (CCGD). Overlapping genes among these were identified as link genes. Functional profiling of the link genes was performed using “g:Profiler” tool to identify enriched Gene Ontology (GO) terms, pathways, miRNAs, transcription factors, and human phenotype ontology terms. Protein-protein interaction (PPI) network was constructed for the link genes using the “STRING” tool, hub nodes were identified as key candidate genes, and functionally enriched terms were determined. Results. The gene expression dataset GEO20151 was downloaded, and 589 DEGs were identified through differential analysis. 886 candidate gastric cancer genes were identified in the CGGD database. Among these, 36 overlapping genes were identified as the link genes. Enriched GO terms included molecular function “enzyme building,” biological process “protein folding,’” cellular components related to membrane-bound organelles, transcription factors ER71 and Sp1, miRNAs miR580 and miR155, and several human phenotype ontology terms including squamous epithelium of esophagus. The PPI network contained 36 nodes and 53 edges, where the top nodes included PH4 and CANX, and functional terms related to intracellular membrane trafficking were enriched. Conclusion. F nucleatum-induced neutrophil transcriptional activation may be implicated in gastric cancer via several candidate genes including DNAJB1, EHD1, IER2, CANX, and PH4B. Functional analysis revealed membrane-bound organelle dysfunction, intracellular trafficking, transcription factors ER71 and Sp1, and miRNAs miR580 and miR155 as other candidate mechanisms, which should be investigated in experimental studies.
14
Ji, Suk, Ji Eun Shin, Young Sook Kim, Ju-Eun Oh, Byung-Moo Min, and Youngnim Choi. "Toll-Like Receptor 2 and NALP2 Mediate Induction of Human Beta-Defensins by Fusobacterium nucleatum in Gingival Epithelial Cells." Infection and Immunity 77, no. 3 (December 22, 2008): 1044–52. http://dx.doi.org/10.1128/iai.00449-08.
Full textAbstract:
ABSTRACT We previously reported that infection by Fusobacterium nucleatum strongly induced the expression of both human beta-defensin 2 (HBD-2) and HBD-3 by gingival epithelial cells. The aim of this study was to characterize the pattern recognition receptors (PRRs) and regulatory mechanisms involved in the induction of HBD-2 and -3 expression by F. nucleatum in gingival epithelial cells. Immortalized human gingival epithelial HOK-16B cells were infected with live or heat-killed F. nucleatum, and the expression of HBDs and interleukin-8 (IL-8) was examined by real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, respectively. Live, but not heat-killed, F. nucleatum invaded HOK-16B cells, as seen by confocal microscopy and flow cytometry. Live F. nucleatum induced both HBD-2 and -3 efficiently, whereas heat-killed bacteria induced only HBD-3 at a reduced level. Knockdown of NACHT-LRR- and pyrin domain-containing protein 2 (NALP2), the most abundant intracellular PRR in HOK-16B cells, by RNA interference (RNAi) significantly reduced the induction of HBD-3 but not HBD-2 and IL-8. In addition, knockdown of Toll-like receptor 2 (TLR2) by RNAi reduced the upregulation of HBD-2 and -3 but not IL-8. Heat-killed F. nucleatum was hindered in its ability to activate TLR2 and JNK signaling pathways. Theses data show that TLR2 and NALP2 mediate the induction of HBDs by F. nucleatum in gingival epithelial cells, but thresholds for the two HBD genes are different.
15
Hung, Shu-Chen, Pei-Rong Huang, Fiona Q. Bui, and David Ojcius. "NLRX1 modulates the balance between NLRP3 inflammasome activation and NF-kB signaling during Fusobacterium nucleatum infection." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 62.1. http://dx.doi.org/10.4049/jimmunol.196.supp.62.1.
Full textAbstract:
Abstract NOD-like receptors (NLRs) play an important role in regulation of host innate immunity, yet their role in periodontitis remains to be defined. NLRX1, a member of the NLR family that localizes to mitochondria, modulates mitochondrial ROS (mROS) generation. mROS has been shown to activate the NLRP3 inflammasome, yet the role of NLRX1 in NLRP3 inflammasome activation has not been examined. In this study, we revealed the mechanism by which NLRX1 positively regulates ATP-elicited NLRP3 inflammasome activation through mROS in gingival epithelial cells (GECs). Fluorescence microscopy showed that depletion of NLRX1 by shRNA attenuates ATP-induced mROS generation and redistribution of the NLRP3 inflammasome adaptor protein, ASC. Furthermore, depletion of NLRX1 inhibits Fusobacterium nucleatum infection-activated caspase-1, suggesting that it also inhibits the NLRP3 inflammasome. Therefore, we propose that NLRX1 may promote F. nucleatum-caused dysregulated pro-inflammatory responses in periodontitis. On the other hand, the mechanism by which F. nucleatum infection-induces IL-8 expression is still unclear. We showed that NLRX1 also acts as a negative regulator in NF-kB signaling to modulate IL-8 expression. Thus, NLRX1 stimulates detection of the pathogen F. nucleatum via the inflammasome, while dampening cytokine production. We expect that commensals should not activate the inflammasome, but NLRX1 should still decrease their ability to stimulate inflammation. We conclude that NLRX1 may act as a potential switch in regards to the virulence of F. nucleatum in healthy or diseased oral cavity.
16
Nogueira, Andressa V. B., Marjan Nokhbehsaim, Anna Damanaki, Sigrun Eick, Svenja Beisel-Memmert, Christian Kirschneck, Agnes Schröder, et al. "Effect of Bacterial Infection on Ghrelin Receptor Regulation in Periodontal Cells and Tissues." International Journal of Molecular Sciences 23, no. 6 (March 11, 2022): 3039. http://dx.doi.org/10.3390/ijms23063039.
Full textAbstract:
The effect of bacterial infection on the expression of growth hormone secretagogue receptor (GHS-R) was investigated in periodontal cells and tissues, and the actions of ghrelin were evaluated. GHS-R was assessed in periodontal tissues of rats with and without periodontitis. Human gingival fibroblasts (HGFs) were exposed to Fusobacterium nucleatum in the presence and absence of ghrelin. GHS-R expression was determined by real-time PCR and immunocytochemistry. Furthermore, wound healing, cell viability, proliferation, and migration were evaluated. GHS-R expression was significantly higher at periodontitis sites as compared to healthy sites in rat tissues. F. nucleatum significantly increased the GHS-R expression and protein level in HGFs. Moreover, ghrelin significantly abrogated the stimulatory effects of F. nucleatum on CCL2 and IL-6 expressions in HGFs and did not affect cell viability and proliferation significantly. Ghrelin stimulated while F. nucleatum decreased wound closure, probably due to reduced cell migration. Our results show original evidence that bacterial infection upregulates GHS-R in rat periodontal tissues and HGFs. Moreover, our study shows that ghrelin inhibited the proinflammatory actions of F. nucleatum on HGFs without interfering with cell viability and proliferation, suggesting that ghrelin and its receptor may act as a protective molecule during bacterial infection on periodontal cells.
17
Kim, D. J., J. H. Rho, B. H. Woo, J. Y. Joo, J. Y. Lee, J. M. Song, J. H. Lee, and H. R. Park. "Periodontal Pathogens Modulate Lipid Flux via Fatty Acid Binding Protein 4." Journal of Dental Research 98, no. 13 (October 17, 2019): 1511–20. http://dx.doi.org/10.1177/0022034519880824.
Full textAbstract:
A strong correlation between chronic periodontitis and systemic diseases (e.g., cardiovascular disease, metabolic disorders) has been suggested for several decades. However, the evidence supporting this correlation is restricted primarily to epidemiologic studies, with only a few experimental outcomes confirming such a correlation and providing information about the underlying molecular mechanisms. To reveal a correlation between periodontitis and systemic diseases as well as a relevant molecular pathway, we investigated the effects of Porphyromonas gingivalis and Fusobacterium nucleatum, which play roles in chronic periodontitis progression, on Raw264.7 and THP-1 macrophages. Infection with P. gingivalis or F. nucleatum significantly induced the expression of fatty acid binding protein 4 (FABP4), one of the most important adipokines that play a role in the progression of systemic diseases such as atherosclerosis and type 2 diabetes. Periodontal pathogen–induced FABP4 expression in macrophages promoted lipid uptake by these cells, as demonstrated by the diminished lipid accumulation in cells treated with an FABP4 inhibitor, BMS309403, or with knockdown of FABP4 expression. This periodontal pathogen–induced FABP4 expression was dependent on the JNK pathway, and JNK inhibition reduced lipid uptake by reducing FABP4 expression. Serum levels of antibodies against P. gingivalis correlated with serum FABP4 levels in humans, whereas no association occurred between F. nucleatum antibody titers and FABP4 levels. To our knowledge, this report is the first to experimentally demonstrate that periodontal pathogens stimulate lipid uptake in macrophages by modulating FABP4 expression. These findings strongly support the hypothesis that periodontitis may affect the progression of various systemic diseases.
18
Asai, Y., Y. Ohyama, Y. Taiji, Y. Makimura, R. Tamai, M. Hashimoto, and T. Ogawa. "Treponema medium Glycoconjugate Inhibits Activation of Human Gingival Fibroblasts Stimulated with Phenol-Water Extracts of Periodontopathic Bacteria." Journal of Dental Research 84, no. 5 (May 2005): 456–61. http://dx.doi.org/10.1177/154405910508400511.
Full textAbstract:
Oral treponemes are well-known as causative agents of periodontal diseases; however, the details have not been fully clarified. Here, we examined the effects of Treponema medium glycoconjugate on the activation of human gingival fibroblasts using phenol-water extracts from Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum subsp. nucleatum, and Actinobacillus actinomycetemcomitans. The phenol-water extracts activated human gingival fibroblasts to mediate IL-8 production, as well as IL-8 mRNA expression, phosphorylation of p38 mitogen-activated protein kinase, and expression of intercellular adhesion molecule-1. T. medium glycoconjugate exhibited no activation of human gingival fibroblasts, while phenol-water extract-induced activation of human gingival fibroblasts was clearly inhibited by T. medium glycoconjugate. Furthermore, binding of biotinylated phenol-water extracts to CD14 in the presence of LPS-binding protein was blocked with T. medium glycoconjugate. These results suggest that T. medium glycoconjugate has an inhibitory effect on host cell activation by periodontopathic bacteria caused by binding to CD14- and LPS-binding protein.
19
Haake, Susan Kinder, and Xiurong Wang. "Cloning and expression of FomA, the major outer-membrane protein gene from fusobacterium nucleatum T18." Archives of Oral Biology 42, no. 1 (January 1997): 19–24. http://dx.doi.org/10.1016/s0003-9969(96)00105-7.
Full text
20
Al-Ahmad, Ali, Kira Wollensak, Sibylle Rau, Diana Lorena Guevara Solarte, Stefan Paschke, Karen Lienkamp, and Ori Staszewski. "How Do Polymer Coatings Affect the Growth and Bacterial Population of a Biofilm Formed by Total Human Salivary Bacteria?—A Study by 16S-RNA Sequencing." Microorganisms 9, no. 7 (July 1, 2021): 1427. http://dx.doi.org/10.3390/microorganisms9071427.
Full textAbstract:
Antimicrobial surface modifications are required to prevent biomaterial-associated biofilm infections, which are also a major concern for oral implants. The aim of this study was to evaluate the influence of three different coatings on the biofilm formed by human saliva. Biofilms grown from human saliva on three different bioactive poly(oxanorbornene)-based polymer coatings (the protein-repellent PSB: poly(oxanorbornene)-based poly(sulfobetaine), the protein-repellent and antimicrobial PZI: poly(carboxyzwitterion), and the mildly antimicrobial and protein-adhesive SMAMP: synthetic mimics of antimicrobial peptides) were analyzed and compared with the microbial composition of saliva, biofilms grown on uncoated substrates, and biofilms grown in the presence of chlorhexidine digluconate. It was found that the polymer coatings significantly reduced the amount of adherent bacteria and strongly altered the microbial composition, as analyzed by 16S RNA sequencing. This may hold relevance for maintaining oral health and the outcome of oral implants due to the existing synergism between the host and the oral microbiome. Especially the reduction of some bacterial species that are associated with poor oral health such as Tannerella forsythia and Fusobacterium nucleatum (observed for PSB and SMAMP), and Prevotella denticola (observed for all coatings) may positively modulate the oral biofilm, including in situ.
21
Hasegawa, Yoshiaki, Jeffrey J. Mans, Song Mao, M. Cecilia Lopez, Henry V. Baker, Martin Handfield, and Richard J. Lamont. "Gingival Epithelial Cell Transcriptional Responses to Commensal and Opportunistic Oral Microbial Species." Infection and Immunity 75, no. 5 (February 16, 2007): 2540–47. http://dx.doi.org/10.1128/iai.01957-06.
Full textAbstract:
ABSTRACT Transcriptional profiling and ontology tools were utilized to define the biological pathways of gingival epithelial cells modulated by coculture with the oral commensal Streptococcus gordonii and the opportunistic commensal Fusobacterium nucleatum. Overall, F. nucleatum and S. gordonii perturbed the gingival epithelial cell transcriptome much less significantly than the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans perturbed the transcriptome, indicating that there was a greater degree of host adaptation by the commensal species (M. Handfield, J. J. Mans, G. Zheng, M. C. Lopez, S. Mao, A. Progulske-Fox, G. Narasimhan, H. V. Baker, and R. J. Lamont, Cell. Microbiol. 7:811-823, 2005). The biological pathways significantly impacted by F. nucleatum and S. gordonii included the mitogen-activated protein kinase (MAPK) and Toll-like receptor signaling pathways. Differential regulation of GADD45 and DUSP4, key components of the MAPK pathway, was confirmed at the protein level by Western blotting. Modulation of the MAPK pathway is likely to affect host cell proliferation and differentiation. In addition, both the MAPK and Toll-like receptor pathways ultimately converge on cytokine gene expression. An enzyme-linked immunosorbent assay of secreted interleukin-6 (IL-6) and IL-8 demonstrated that F. nucleatum induced production of these cytokines, whereas S. gordonii inhibited secretion from the epithelial cells. Stimulation of secretion of proinflammatory cytokines from epithelial cells may reflect the invasive phenotype of F. nucleatum and contribute to the greater pathogenic potential of F. nucleatum than of S. gordonii.
22
Zhang, Qian, Shuipeng Yu, Meilin Hu, Zhiyang Liu, Pei Yu, Changyi Li, and Xi Zhang. "Antibacterial and Anti-Inflammatory Properties of Peptide KN-17." Microorganisms 10, no. 11 (October 26, 2022): 2114. http://dx.doi.org/10.3390/microorganisms10112114.
Full textAbstract:
Peri-implantitis, an infectious disease originating from dental biofilm that forms around dental implants, which causes the loss of both osseointegration and bone tissue. KN-17, a truncated cecropin B peptide, demonstrated efficacy against certain bacterial strains associated with peri-implantitis. This study aimed to assess the antibacterial and anti-inflammatory properties and mechanisms of KN-17. The effects of KN-17 on oral pathogenic bacteria were assessed by measuring its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Moreover, the cytotoxicity and anti-inflammatory effects of KN-17 were evaluated. KN-17 inhibited the growth of Streptococcus gordonii and Fusobacterium nucleatum during in vitro biofilm formation and possessed low toxicity to hBMSCs cells. KN-17 also caused RAW264.7 macrophages to transform from M1 to M2 by downregulating pro-inflammatory and upregulating anti-inflammatory factors. It inhibited the NF-κB signaling pathway by reducing IκBα and P65 protein phosphorylation while promoting IκBα degradation and nuclear P65 translocation. KN-17 might be an efficacious prophylaxis against peri-implant inflammation.
23
Yoshida, Yasuo, Shuntaro Ito, Masaharu Kamo, Yuichiro Kezuka, Haruki Tamura, Kazushi Kunimatsu, and Hirohisa Kato. "Production of hydrogen sulfide by two enzymes associated with biosynthesis of homocysteine and lanthionine in Fusobacterium nucleatum subsp. nucleatum ATCC 25586." Microbiology 156, no. 7 (July 1, 2010): 2260–69. http://dx.doi.org/10.1099/mic.0.039180-0.
Full textAbstract:
Fusobacterium nucleatum produces a large amount of the toxic metabolite hydrogen sulfide in the oral cavity. Here, we report the molecular basis of F. nucleatum H2S production, which is associated with two different enzymes: the previously reported Cdl (Fn1220) and the newly identified Lcd (Fn0625). SDS-PAGE analysis with activity staining revealed that crude enzyme extracts from F. nucleatum ATCC 25586 contained three major H2S-producing proteins. Two of the proteins with low molecular masses migrated similarly to purified Fn0625 and Fn1220. Their kinetic values suggested that Fn0625 had a lower enzymic capacity to produce H2S from l-cysteine (∼30 %) than Fn1220. The Fn0625 protein degraded a variety of substrates containing βC–S linkages to produce ammonia, pyruvate and sulfur-containing products. Unlike Fn0625, Fn1220 produced neither pyruvate nor ammonia from l-cysteine. Reversed-phase HPLC separation and mass spectrometry showed that incubation of l-cysteine with Fn1220 produced H2S and an uncommon amino acid, lanthionine, which is a natural constituent of the peptidoglycans of F. nucleatum ATCC 25586. In contrast, most of the sulfur-containing substrates tested, except l-cysteine, were not used by Fn1220. Real-time PCR analysis demonstrated that the fn1220 gene showed several-fold higher expression than fn0625 and housekeeping genes in exponential-phase cultures of F. nucleatum. Thus, we conclude that Fn0625 and Fn1220 produce H2S in distinct manners: Fn0625 carries out β-elimination of l-cysteine to produce H2S, pyruvate and ammonia, whereas Fn1220 catalyses the β-replacement of l-cysteine to produce H2S and lanthionine, the latter of which may be used for peptidoglycan formation in F. nucleatum.
24
Memmert, S., A. Damanaki, A. V. B. Nogueira, S. Eick, M. Nokhbehsaim, A. K. Papadopoulou, A. Till, et al. "Role of Cathepsin S in Periodontal Inflammation and Infection." Mediators of Inflammation 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/4786170.
Full textAbstract:
Cathepsin S is a cysteine protease and regulator of autophagy with possible involvement in periodontitis. The objective of this study was to investigate whether cathepsin S is involved in the pathogenesis of periodontal diseases. Human periodontal fibroblasts were cultured under inflammatory and infectious conditions elicited by interleukin-1β and Fusobacterium nucleatum, respectively. An array-based approach was used to analyze differential expression of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. In vivo, gingival tissue biopsies from rats with ligature-induced periodontitis and from periodontitis patients were also analyzed at transcriptional and protein levels. Multiple gene expression changes due to interleukin-1β and F. nucleatum were observed in vitro. Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival biopsies from rats with experimental periodontitis was found in vivo, as compared to that from control. Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. Our findings provide original evidence that cathepsin S is increased in periodontal cells and tissues under inflammatory and infectious conditions, suggesting a critical role of this autophagy-associated molecule in the pathogenesis of periodontitis.
25
Zilm, Peter S., Alex Mira, Christopher J. Bagley, and Anthony H. Rogers. "Effect of alkaline growth pH on the expression of cell envelope proteins in Fusobacterium nucleatum." Microbiology 156, no. 6 (June 1, 2010): 1783–94. http://dx.doi.org/10.1099/mic.0.035881-0.
Full textAbstract:
Fusobacterium nucleatum is a Gram-negative anaerobic organism that plays a central role in the development of periodontal diseases. The progression of periodontitis is associated with a rise in pH of the gingival sulcus which promotes the growth and expression of virulence factors by periodontopathic bacteria. We have previously reported that the expression of specific cytoplasmic proteins is altered by a shift in growth pH. In the present study we have compared cell envelope protein expression of F. nucleatum during chemostat growth at pH 7.2 and 7.8. From a total of 176 proteins resolved from the cell envelope, 15 were found to have altered expression in response to an increase in growth pH and were identified by MS. Upregulated proteins included an outer membrane porin which has been identified as playing a role in virulence, a periplasmic chaperone which assists in the folding of outer membrane proteins, and a transporter thought to be involved with iron uptake. Proteins downregulated at pH 7.8 were consistent with our previous findings that the bacterium reduces its catabolism of energy-yielding substrates in favour of energy-storage pathways. Among the downregulated proteins, two transporters which are involved in the uptake of C4 dicarboxylates and phosphate were identified. A putative protease and an enzyme associated with the metabolism of glutamate were also identified. A high proportion of the cell envelope proteins suggested by these data to play a role in the organism's response to alkaline growth pH may have arisen by lateral gene transfer. This would support the hypothesis that genes that provide an ability to adapt to the changing conditions of the oral environment may be readily shared between oral bacteria.
26
Gursoy, Ulvi K., Marja Pöllänen, Eija Könönen, and Veli-Jukka Uitto. "A Novel Organotypic Dento-Epithelial Culture Model: Effect of Fusobacterium nucleatum Biofilm on B-Defensin-2, -3, and LL-37 Expression." Journal of Periodontology 83, no. 2 (February 2012): 242–47. http://dx.doi.org/10.1902/jop.2011.110177.
Full text
27
Krisanaprakornkit, Suttichai, Janet R. Kimball, Aaron Weinberg, Richard P. Darveau, Brian W. Bainbridge, and Beverly A. Dale. "Inducible Expression of Human β-Defensin 2 byFusobacterium nucleatum in Oral Epithelial Cells: Multiple Signaling Pathways and Role of Commensal Bacteria in Innate Immunity and the Epithelial Barrier." Infection and Immunity 68, no. 5 (May 1, 2000): 2907–15. http://dx.doi.org/10.1128/iai.68.5.2907-2915.2000.
Full textAbstract:
ABSTRACT Human gingival epithelial cells (HGE) express two antimicrobial peptides of the β-defensin family, human β-defensin 1 (hBD-1) and hBD-2, as well as cytokines and chemokines that contribute to innate immunity. In the present study, the expression and transcriptional regulation of hBD-2 was examined. HBD-2 mRNA was induced by cell wall extract of Fusobacterium nucleatum, an oral commensal microorganism, but not by that of Porphyromonas gingivalis, a periodontal pathogen. HBD-2 mRNA was also induced by the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) and phorbol myristate acetate (PMA), an epithelial cell activator. HBD-2 mRNA was also expressed in 14 of 15 noninflamed gingival tissue samples. HBD-2 peptide was detected by immunofluorescence in HGE stimulated with F. nucleatum cell wall, consistent with induction of the mRNA by this stimulant. Kinetic analysis indicates involvement of multiple distinct signaling pathways in the regulation of hBD-2 mRNA; TNF-α and F. nucleatum cell wall induced hBD-2 mRNA rapidly (2 to 4 h), while PMA stimulation was slower (∼10 h). In contrast, each stimulant induced interleukin 8 (IL-8) within 1 h. The role of TNF-α as an intermediary in F. nucleatum signaling was ruled out by addition of anti-TNF-α that did not inhibit hBD-2 induction. However, inhibitor studies show that F. nucleatum stimulation of hBD-2 mRNA requires both new gene transcription and new protein synthesis. Bacterial lipopolysaccharides isolated from Escherichia coli andF. nucleatum were poor stimulants of hBD-2, although they up-regulated IL-8 mRNA. Collectively, our findings show inducible expression of hBD-2 mRNA via multiple pathways in HGE in a pattern that is distinct from that of IL-8 expression. We suggest that different aspects of innate immune responses are differentially regulated and that commensal organisms have a role in stimulating mucosal epithelial cells in maintaining the barrier that contributes to homeostasis and host defense.
28
Rath-Deschner, Birgit, Svenja Memmert, Anna Damanaki, Marjan Nokhbehsaim, Sigrun Eick, Joni A. Cirelli, Werner Götz, James Deschner, Andreas Jäger, and Andressa V. B. Nogueira. "CXCL1, CCL2, and CCL5 modulation by microbial and biomechanical signals in periodontal cells and tissues—in vitro and in vivo studies." Clinical Oral Investigations 24, no. 10 (March 2, 2020): 3661–70. http://dx.doi.org/10.1007/s00784-020-03244-1.
Full textAbstract:
Abstract Objectives This study was established to investigate whether the chemokines CXCL1, CCL2, and CCL5 are produced in periodontal cells and tissues and, if so, whether their levels are regulated by microbial and/or mechanical signals. Materials and methods The chemokine expression and protein levels in gingival biopsies from patients with and without periodontitis were analyzed by RT-PCR and immunohistochemistry. The chemokines were also analyzed in gingival biopsies from rats subjected to experimental periodontitis and/or orthodontic tooth movement. Additionally, chemokine levels were determined in periodontal fibroblasts exposed to the periodontopathogen Fusobacterium nucleatum and mechanical forces by RT-PCR and ELISA. Results Higher CXCL1, CCL2, and CCL5 levels were found in human and rat gingiva from sites of periodontitis as compared with periodontally healthy sites. In the rat experimental periodontitis model, the bacteria-induced upregulation of these chemokines was significantly counteracted by orthodontic forces. In vitro, F. nucleatum caused a significant upregulation of all chemokines at 1 day. When the cells were subjected simultaneously to F. nucleatum and mechanical forces, the upregulation of chemokines was significantly inhibited. The transcriptional findings were paralleled at protein level. Conclusions This study provides original evidence in vitro and in vivo that the chemokines CXCL1, CCL2, and CCL5 are regulated by both microbial and mechanical signals in periodontal cells and tissues. Furthermore, our study revealed that biomechanical forces can counteract the stimulatory actions of F. nucleatum on these chemokines. Clinical relevance Mechanical loading might aggravate periodontal infection by compromising the recruitment of immunoinflammatory cells.
29
Ali Mohammed, Marwan Mansoor, Veronika Kuchařová Pettersen, Audun H. Nerland, Harald G. Wiker, and Vidar Bakken. "Label-free quantitative proteomic analysis of the oral bacteria Fusobacterium nucleatum and Porphyromonas gingivalis to identify protein features relevant in biofilm formation." Anaerobe 72 (December 2021): 102449. http://dx.doi.org/10.1016/j.anaerobe.2021.102449.
Full text
30
Feng, Yu-yang, Dong-zhu Zeng, Ya-nan Tong, Xiao-xue Lu, Guo-dong Dun, Bin Tang, Zhu-jun Zhang, et al. "Alteration of microRNA-4474/4717 expression and CREB-binding protein in human colorectal cancer tissues infected with Fusobacterium nucleatum." PLOS ONE 14, no. 4 (April 5, 2019): e0215088. http://dx.doi.org/10.1371/journal.pone.0215088.
Full text
31
Huang, George T. J., Daniel Kim, Jonathan K. H. Lee, Howard K. Kuramitsu, and Susan Kinder Haake. "Interleukin-8 and Intercellular Adhesion Molecule 1 Regulation in Oral Epithelial Cells by Selected Periodontal Bacteria: Multiple Effects of Porphyromonas gingivalis via Antagonistic Mechanisms." Infection and Immunity 69, no. 3 (March 1, 2001): 1364–72. http://dx.doi.org/10.1128/iai.69.3.1364-1372.2001.
Full textAbstract:
ABSTRACT Interaction of bacteria with mucosal surfaces can modulate the production of proinflammatory cytokines and adhesion molecules produced by epithelial cells. Previously, we showed that expression of interleukin-8 (IL-8) and intercellular adhesion molecule 1 (ICAM-1) by gingival epithelial cells increases following interaction with several putative periodontal pathogens. In contrast, expression of IL-8 and ICAM-1 is reduced after Porphyromonas gingivalis ATCC 33277 challenge. In the present study, we investigated the mechanisms that govern the regulation of these two molecules in bacterially infected gingival epithelial cells. Experimental approaches included bacterial stimulation of gingival epithelial cells by either a brief challenge (1.5 to 2 h) or a continuous coculture throughout the incubation period. The kinetics of IL-8 and ICAM-1 expression following brief challenge were such that (i) secretion of IL-8 by gingival epithelial cells reached its peak 2 h following Fusobacterium nucleatum infection whereas it rapidly decreased within 2 h after P. gingivalis infection and remained decreased up to 30 h and (ii) IL-8 and ICAM-1 mRNA levels were up-regulated rapidly 2 to 4 h postinfection and then decreased to basal levels 8 to 20 h after infection with either Actinobacillus actinomycetemcomitans, F. nucleatum, or P. gingivalis. Attenuation of IL-8 secretion was facilitated by adherent P. gingivalis strains. The IL-8 secreted from epithelial cells after F. nucleatum stimulation could be down-regulated by subsequent infection with P. gingivalisor its culture supernatant. Although these results suggested that IL-8 attenuation at the protein level might be associated with P. gingivalis proteases, the Arg- and Lys-gingipain proteases did not appear to be solely responsible for IL-8 attenuation. In addition, while P. gingivalis up-regulated IL-8 mRNA expression, this effect was overridden when the bacteria were continuously cocultured with the epithelial cells. The IL-8 mRNA levels in epithelial cells following sequential challenge with P. gingivalis andF. nucleatum and vice versa were approximately identical and were lower than those following F. nucleatum challenge alone and higher than control levels or those following P. gingivalis challenge alone. Thus, together with the protease effect, P. gingivalis possesses a powerful strategy to ensure the down-regulation of IL-8 and ICAM-1.
32
Wu, Yixian, Songhe Guo, Fangfang Chen, Yiqiu Li, Yuying Huang, Wanli Liu, and Ge Zhang. "Fn-Dps, a novel virulence factor of Fusobacterium nucleatum, disrupts erythrocytes and promotes metastasis in colorectal cancer." PLOS Pathogens 19, no. 1 (January 24, 2023): e1011096. http://dx.doi.org/10.1371/journal.ppat.1011096.
Full textAbstract:
Fusobacterium nucleatum (Fn) is a critical colorectal cancer (CRC)-associated bacterium. DNA hunger/stationary phase protective proteins (Dps) are bacterial ferritins that protect DNA from oxidative stress. However, little is known about the regulatory roles of Fn-Dps towards host cellular functions. Here, we identified Fn-Dps from the culture supernatant of Fn by mass spectrometry, and prepared the recombinant of Fn-Dps protein. We show a novel virulence protein of Fn, Fn-Dps, which lyses and disrupts erythrocytes by the competition for iron acquisition. Also, Fn-Dps facilitates intracellular survival of Fn in macrophages by upregulating the expression of the chemokine CCL2/CCL7. In addition, Fn-Dps can elicit a strong humoral immune response, and mucosal immunization with Fn-Dps conferred protection against Fn in the intestinal tract. Moreover, a high level of anti-Fn-Dps antibody was prevalent in populations, and elevated anti-Fn-Dps antibody levels were observed in CRC patients. Furthermore, Fn-Dps promotes the migration of CRC cells via the CCL2/CCL7-induced epithelial-mesenchymal transition (EMT) and promotes CRC metastasis in vivo.
33
Karaca, Basar, Ozan Haliscelik, Mervi Gursoy, Fadime Kiran, Vuokko Loimaranta, Eva Söderling, and Ulvi Kahraman Gursoy. "Analysis of Chemical Structure and Antibiofilm Properties of Exopolysaccharides from Lactiplantibacillus plantarum EIR/IF-1 Postbiotics." Microorganisms 10, no. 11 (November 7, 2022): 2200. http://dx.doi.org/10.3390/microorganisms10112200.
Full textAbstract:
Previous studies have indicated that the exopolysaccharides of lactic acid bacteria exhibit antibiofilm activity against non-oral bacteria by preventing their initial adhesion to surfaces and by downregulating the expression of genes responsible for their biofilm formation. The aims of this study were to (1) characterize the exopolysaccharides (EPSs) of Lactobacillus plantarum EIR/IF-1 postbiotics, (2) test their antibiofilm effect on dual biofilms, and (3) evaluate their bacterial auto-aggregation, co-aggregation, and hydrocarbon-binding inhibitory activity. The EPSs were characterized by FTIR, HPLC, and thermogravimetric analysis. Bacterial auto- and co-aggregation were tested by Kolenbrander’s method and hydrocarbon binding was tested by Rosenberg’s method. Dual biofilms were formed by culturing Fusobacterium nucleatum ATCC 25586 with one of the following bacteria: Prevotella denticola ATCC 33185, P. denticola AHN 33266, Porphyromonas gingivalis ATCC 33277, P. gingivalis AHN 24155, and Filifactor alocis ATCC 35896. The EPSs contained fractions with different molecular weights (51 and 841 kDa) and monosaccharides of glucose, galactose, and fructose. The EPSs showed antibiofilm activity in all the biofilm models tested. The EPSs may have inhibited bacterial aggregation and binding to hydrocarbons by reducing bacterial hydrophobicity. In conclusion, the EPSs of L. plantarum EIR/IF-1, which consists of two major fractions, exhibited antibiofilm activity against oral bacteria, which can be explained by the inhibitory effect of EPSs on the auto-aggregation and co-aggregation of bacteria and their binding to hydrocarbons.
34
Bhattacharyya, Sanghamitra, Santosh K. Ghosh, Bhumika Shokeen, Betty Eapan, Renate Lux, Janna Kiselar, Stanley Nithianantham, et al. "FAD-I, a Fusobacterium nucleatum Cell Wall-Associated Diacylated Lipoprotein That Mediates Human Beta Defensin 2 Induction through Toll-Like Receptor-1/2 (TLR-1/2) and TLR-2/6." Infection and Immunity 84, no. 5 (February 29, 2016): 1446–56. http://dx.doi.org/10.1128/iai.01311-15.
Full textAbstract:
We previously identified a cell wall-associated protein fromFusobacterium nucleatum, a Gram-negative bacterium of the oral cavity, that induces human beta defensin 2 (hBD-2) in primary human oral epithelial cells (HOECs) and designated it FAD-I (Fusobacterium-associateddefensininducer). Here, we report differential induction of hBD-2 by different strains ofF. nucleatum; ATCC 25586 and ATCC 23726 induce significantly more hBD-2 mRNA than ATCC 10953. Heterologous expression of plasmid-bornefadIfrom the highly hBD-2-inducing strains in a ΔfadImutant of ATCC 10953 resulted in hBD-2 induction to levels comparable to those of the highly inducing strains, indicating that FAD-I is the principalF. nucleatumagent for hBD-2 induction in HOECs. Moreover, anti-FAD-I antibodies blockedF. nucleatuminduction of hBD-2 by more than 80%. Recombinant FAD-I (rFAD-I) expressed inEscherichia colitriggered levels of hBD-2 transcription and peptide release in HOECs similar to those of native FAD-I (nFAD-I) isolated fromF. nucleatumATCC 25586. Tandem mass spectrometry revealed a diacylglycerol modification at the cysteine residue in position 16 for both nFAD-I and rFAD-I. Cysteine-to-alanine substitution abrogated FAD-I's ability to induce hBD-2. Finally, FAD-I activation of hBD-2 expression was mediated via both Toll-like receptor-1/2 (TLR-1/2) and TLR-2/6 heterodimerization. Microbial molecules like FAD-I may be utilized in novel therapeutic ways to bolster the host innate immune response at mucosal surfaces.
35
Baqui, A. A. M. A., Timothy F. Meiller, Jennifer J. Chon, Been-Foo Turng, and William A. Falkler. "Granulocyte-Macrophage Colony-Stimulating Factor Amplification of Interleukin-1β and Tumor Necrosis Factor Alpha Production in THP-1 Human Monocytic Cells Stimulated with Lipopolysaccharide of Oral Microorganisms." Clinical Diagnostic Laboratory Immunology 5, no. 3 (May 1, 1998): 341–47. http://dx.doi.org/10.1128/cdli.5.3.341-347.1998.
Full textAbstract:
ABSTRACT Cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) play important roles in inflammatory processes, including exacerbation of periodontal diseases, one of the most common complications in patients who undergo this therapy. A human monocyte cell line (THP-1) was utilized to investigate IL-1β and TNF-α production following GM-CSF supplementation with lipopolysaccharide (LPS) from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. LPS ofP. gingivalis or F. nucleatum was prepared by a phenol-water extraction method and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and determination of total protein and endotoxin contents. Resting THP-1 cells were treated with LPS of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) by using different concentrations for various time periods. Production of IL-1β and TNF-α in THP-1 cells was measured by solid-phase enzyme-linked immunosorbent assay. Reverse transcription (RT)-PCR was used to evaluate the gene expression of resting and treated THP-1 cells. IL-1β was not detected in untreated THP-1 cells. IL-1β production was, however, stimulated sharply at 4 h. GM-CSF amplified IL-1β production in THP-1 cells treated with LPS from both oral anaerobes. No IL-1β-specific mRNA transcript was detected in untreated THP-1 cells. However, IL-1β mRNA was detected by RT-PCR 2 h after stimulation of THP-1 cells with LPS from both organisms. GM-CSF did not shorten the IL-1β transcriptional activation time. GM-CSF plus F. nucleatum or P. gingivalis LPS activated THP-1 cells to produce a 1.6-fold increase in TNF-α production at 4 h over LPS stimulation alone. These investigations with the in vitro THP-1 model indicate that there may be an increase in the cellular immune response to oral endotoxin following GM-CSF therapy, as evidenced by production of the tissue-reactive cytokines IL-1β and TNF-α.
36
Yun, In-Gyeong, Sun-Hee Ahn, Weon-Jong Yoon, Chang Kim, Yun Lim, Joong-Ki Kook, Seunggon Jung, Choong-Ho Choi, and Tae-Hoon Lee. "Litsea japonica Leaf Extract Suppresses Proinflammatory Cytokine Production in Periodontal Ligament Fibroblasts Stimulated with Oral Pathogenic Bacteria or Interleukin-1β." International Journal of Molecular Sciences 19, no. 9 (August 23, 2018): 2494. http://dx.doi.org/10.3390/ijms19092494.
Full textAbstract:
Periodontal disease, a chronic disease caused by bacterial infection, eventually progresses to severe inflammation and bone loss. Regulating excessive inflammation of inflamed periodontal tissues is critical in treating periodontal diseases. The periodontal ligament (PDL) is primarily a connective tissue attachment between the root and alveolar bone. PDL fibroblasts (PDLFs) produce pro-inflammatory cytokines in response to bacterial infection, which could further adversely affect the tissue and cause bone loss. In this study, we determined the ability of Litsea japonica leaf extract (LJLE) to inhibit pro-inflammatory cytokine production in PDLFs in response to various stimulants. First, we found that LJLE treatment reduced lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (interleukin-6 and interleukin-8) mRNA and protein expression in PDLFs without cytotoxicity. Next, we observed the anti-inflammatory effect of LJLE in PDLFs after infection with various oral bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. These anti-inflammatory effects of LJLE were dose-dependent, and the extract was effective following both pretreatment and posttreatment. Moreover, we found that LJLE suppressed the effect of interleukin-1 beta-induced pro-inflammatory cytokine production in PDLFs. Taken together, these results indicate that LJLE has anti-inflammatory activity that could be exploited to prevent and treat human periodontitis by controlling inflammation.
37
Thumbigere Math, V., P. Rebouças, P. A. Giovani, R. M. Puppin-Rontani, R. Casarin, L. Martins, L. Wang, et al. "Periodontitis in Chédiak-Higashi Syndrome: An Altered Immunoinflammatory Response." JDR Clinical & Translational Research 3, no. 1 (August 3, 2017): 35–46. http://dx.doi.org/10.1177/2380084417724117.
Full textAbstract:
Chédiak-Higashi syndrome (CHS), a rare autosomal recessive disorder caused by mutations in the lysosomal trafficking regulator gene (LYST), is associated with aggressive periodontitis. It is suggested that LYST mutations affect the toll-like receptor (TLR)–mediated immunoinflammatory response, leading to frequent infections. This study sought to determine the periodontal status of patients with classic (severe) and atypical (milder) forms of CHS and the immunoregulatory functions of gingival fibroblasts in CHS patients. In contrast to aged-matched healthy controls, atypical (n = 4) and classic (n = 3) CHS patients presented with mild chronic periodontitis with no evidence of gingival ulceration, severe tooth mobility, or premature exfoliation of teeth. As a standard of care, all classic CHS patients had undergone bone marrow transplantation (BMT). Primary gingival fibroblasts obtained from atypical and BMT classic CHS patients displayed higher protein expression of TLR-2 (1.81-fold and 1.56-fold, respectively) and decreased expression of TLR-4 (−2.5-fold and −3.85-fold, respectively) at baseline when compared with healthy control gingival fibroblasts. When challenged with whole bacterial extract of Fusobacterium nucleatum, both atypical and classic CHS gingival fibroblasts failed to up-regulate TLR-2 and TLR-4 expression when compared with their respective untreated groups and control cells. Cytokine multiplex analysis following F. nucleatum challenge showed that atypical CHS gingival fibroblasts featured significantly increased cytokine expression (interleukin [IL]–2, IL-4, IL-5, IL-6, IL-10, IL-12, interferon-γ, tumor necrosis factor–α), whereas classic CHS cells featured similar/decreased cytokine expression when compared with treated control cells. Collectively, these results suggest that LYST mutations in CHS patients affect TLR-2 and TLR-4 expression/function, leading to dysregulated immunoinflammatory response, which in turn may influence the periodontal phenotype noted in CHS patients. Furthermore, our results suggest that atypical CHS patients and classic CHS patients who undergo BMT early in life are less susceptible to aggressive periodontitis and that hematopoietic cells play a critical role in mitigating the risk of aggressive periodontitis in CHS. Knowledge Transfer Statement: Results from this study can be used to create awareness among clinicians and researchers that not all CHS patients exhibit historically reported aggressive periodontitis, especially if they have atypical CHS disease or have received bone marrow transplantation. LYST mutations in CHS patients may affect TLR-2 and TLR-4 expression/function leading to dysregulated immunoinflammatory response, which in turn may influence the periodontal phenotype noted in CHS patients.
38
Aziz, Shahid, Faisal Rasheed, Tayyab Saeed Akhter, Rabaab Zahra, and Simone König. "Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer." Molecules 27, no. 17 (August 24, 2022): 5410. http://dx.doi.org/10.3390/molecules27175410.
Full textAbstract:
(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.
39
Taubman, Martin A., Xiaozhe Han, Karen B. LaRosa, Sigmund S. Socransky, and Daniel J. Smith. "Periodontal Bacterial DNA Suppresses the Immune Response to Mutans Streptococcal Glucosyltransferase." Infection and Immunity 75, no. 8 (May 21, 2007): 4088–96. http://dx.doi.org/10.1128/iai.00623-07.
Full textAbstract:
ABSTRACT Certain CpG motifs found in bacterial DNA enhance immune responses through Toll-like receptor 9 (TLR-9) and may also demonstrate adjuvant properties. Our objective was to determine if DNA from bacteria associated with periodontal disease could affect the immune response to other bacterial antigens in the oral cavity. Streptococcus sobrinus glucosyltransferase (GTF), an enzyme involved in dental caries pathogenesis, was used as a test antigen. Rowett rats were injected with aluminum hydroxide (alum) with buffer, alum-GTF, or alum-GTF together with either Escherichia coli DNA, Fusobacterium nucleatum DNA, or Porphyromonas gingivalis DNA. Contrary to expectation, animals receiving alum-GTF plus bacterial DNA (P. gingivalis in particular) demonstrated significantly reduced serum immunoglobulin G (IgG) antibody, salivary IgA antibody, and T-cell proliferation to GTF compared to animals immunized with alum-GTF alone. A diminished antibody response was also observed after administration of alum-GTF with the P. gingivalis DNA either together or separately, indicating that physical complexing of antigen and DNA was not responsible for the reduction in antibody. Since TLR triggering by DNA induces synthesis of prospective suppressive factors (e.g., suppressor of cytokine signaling [SOCS]), the effects of P. gingivalis DNA and GTF exposure on rat splenocyte production of SOCS family molecules and inflammatory cytokines were investigated in vitro. P. gingivalis DNA significantly up-regulated SOCS1 and SOCS5 expression and down-regulated interleukin-10 expression by cultured splenocytes. These results suggested that DNA from periodontal disease-associated bacteria did not enhance, but in fact suppressed, the immune response to a protein antigen from cariogenic streptococci, potentially through suppressive SOCS components triggered by innate mechanisms.
40
Khan, Saadullah Jan. "Comparative In Silico Investigation of Biofilm vs Planktonic State Protein Expression in Fusobacterium nucleatum." Academia Letters, May 13, 2022. http://dx.doi.org/10.20935/al5312.
Full text
41
Guo, Pin, Zibin Tian, Xinjuan Kong, Lin Yang, Xinzhi Shan, Bingzi Dong, Xueli Ding, et al. "FadA promotes DNA damage and progression of Fusobacterium nucleatum-induced colorectal cancer through up-regulation of chk2." Journal of Experimental & Clinical Cancer Research 39, no. 1 (September 29, 2020). http://dx.doi.org/10.1186/s13046-020-01677-w.
Full textAbstract:
Abstract Background Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to non-modifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of E-cadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to up-regulation of chk2.
42
Zhou, Peng, Xiaoli Li, I.-Hsiu Huang, and Fengxia Qi. "Veillonella Catalase Protects the Growth of Fusobacterium nucleatum in Microaerophilic and Streptococcus gordonii-Resident Environments." Applied and Environmental Microbiology 83, no. 19 (August 4, 2017). http://dx.doi.org/10.1128/aem.01079-17.
Full textAbstract:
ABSTRACT The oral biofilm is a multispecies community in which antagonism and mutualism coexist among friends and foes to keep an ecological balance of community members. The pioneer colonizers, such as Streptococcus gordonii, produce H2O2 to inhibit the growth of competitors, like the mutans streptococci, as well as strict anaerobic middle and later colonizers of the dental biofilm. Interestingly, Veillonella species, as early colonizers, physically interact (coaggregate) with S. gordonii. A putative catalase gene (catA) is found in most sequenced Veillonella species; however, the function of this gene is unknown. In this study, we characterized the ecological function of catA from Veillonella parvula PK1910 by integrating it into the only transformable strain, Veillonella atypica OK5, which is catA negative. The strain (OK5-catA) became more resistant to H2O2. Further studies demonstrated that the catA gene expression is induced by the addition of H2O2 or coculture with S. gordonii. Mixed-culture experiments further revealed that the transgenic OK5-catA strain not only enhanced the growth of Fusobacterium nucleatum, a strict anaerobic periodontopathogen, under microaerophilic conditions, but it also rescued F. nucleatum from killing by S. gordonii. A potential role of catalase in veillonellae in biofilm ecology and pathogenesis is discussed here. IMPORTANCE Veillonella species, as early colonizers, can coaggregate with many bacteria, including the initial colonizer Streptococcus gordonii and periodontal pathogen Fusobacterium nucleatum, during various stages of oral biofilm formation. In addition to providing binding sites for many microbes, our previous study also showed that Veillonella produces nutrients for the survival and growth of periodontal pathogens. These findings indicate that Veillonella plays an important “bridging” role in the development of oral biofilms and the ecology of the human oral cavity. In this study, we demonstrated that the reducing activity of Veillonella can rescue the growth of Fusobacterium nucleatum not only under microaerophilic conditions, but also in an environment in which Streptococcus gordonii is present. Thus, this study will provide a new insight for future studies on the mechanisms of human oral biofilm formation and the control of periodontal diseases.
43
Liu, Hui, Yuxuan Liu, Wei Fan, and Bing Fan. "Fusobacterium nucleatum triggers proinflammatory cell death via Z-DNA binding protein 1 in apical periodontitis." Cell Communication and Signaling 20, no. 1 (December 20, 2022). http://dx.doi.org/10.1186/s12964-022-01005-z.
Full textAbstract:
Abstract Background Z-DNA binding protein 1 (ZBP1) is a vital innate immune sensor that regulates inflammation during pathogen invasion. ZBP1 may contribute to pyroptosis, apoptosis and necroptosis in infectious diseases. In this study, Fusobacterium nucleatum (F. nucleatum) infection caused periapical inflammation through proinflammatory cell death and ZBP1 was involved in regulating the inflammatory activities caused by F. nucleatum infection in apical periodontitis (AP). Methods Human periapical tissues were tested by fluorescent in situ hybridization, immunohistochemical staining, immunofluorescence staining, quantitative real-time PCR (qRT‒PCR) and western blotting. F. nucleatum-infected and F. nucleatum extracellular vesicles (F. nucleatum-EVs)-treated RAW264.7 cells were used to detect the expression of inflammatory cytokines and different cell death mechanisms by qRT‒PCR and western blotting. ZBP1 expression in F. nucleatum-infected tissues and RAW264.7 cells was detected by qRT‒PCR, western blotting, and immunohistochemical and immunofluorescence staining. Furthermore, the expression of ZBP1 was inhibited by siRNA and different cell death pathways, including pyroptosis, apoptosis, and necroptosis, and inflammatory cytokines were measured in F. nucleatum-infected RAW264.7 cells. Results F. nucleatum was detected in AP tissues. F. nucleatum-infected RAW264.7 cells polarized to the M1 phenotype, and this was accompanied by inflammatory cytokine production. High levels of ZBP1 and GSDME (gasdermin E)-mediated pyroptosis, caspase-3-mediated apoptosis and MLKL-mediated necroptosis (PANoptosis) were identified in F. nucleatum-infected tissues and RAW264.7 cells. ZBP1 inhibition reduced inflammatory cytokine secretion and the occurrence of PANoptosis. Conclusion The present study identified a previously unknown role of ZBP1 in regulating F. nucleatum-induced proinflammatory cell death and inflammatory activation.
44
Ding, Qinfeng, Xuecheng Sun, Shuai Cao, Cancan Zhao, Yitong Wang, and Xudong Wang. "Heat-killed Lactobacillus acidophilus mediates Fusobacterium nucleatum induced pro-inflammatory responses in epithelial cells." FEMS Microbiology Letters 368, no. 5 (March 2021). http://dx.doi.org/10.1093/femsle/fnaa160.
Full textAbstract:
Abstract Probiotics is widespreadly used nowadays. However, the safety issue with the use of live probiotics is still a matter of contention. In recent years, an expanding body of evidence supports the beneficial role of heat-killed probiotics in the maintenance of systemic health, whereas the role of these heat-killed bacteria on periodontal health remains unclear. This study aimed to evaluate the effects of heat-killed probiotics on periodontal pathogen virulence and associated mechanisms. We demonstrated that heat-killed Lactobacillus acidophilus was able to coaggregate with Fusobacterium nucleatum, the bridging bacteria of oral biofilm, and inhibit the adhesion and invasion of F. nucleatum, leading to a subsequent elimination of pro-inflammatory cytokine production in oral epithelial cells. This coaggregation further caused a suppression of the virulence gene fap2 expression in F. nucleatum. Therefore, heat-killed L. acidophilus might downregulate the pro-inflammatory cytokine expression in epithelial cells via coaggregation with F. nucleatum and suppression of F. nucleatum fap2 expression, which was the first demonstration that heat-killed probiotics modulate periodontal disease pathogenesis via coaggregation. Collectively, this finding provides new evidence that heat-killed probiotics might exert beneficial effects to periodontal health by coaggregating with periodontal pathogens and modulating their virulence.
45
Yang, Ruiqi, Tingjun Liu, Chunfeng Pang, Yanling Cai, Zhengmei Lin, Lihong Guo, and Xi Wei. "The Regulatory Effect of Coaggregation Between Fusobacterium nucleatum and Streptococcus gordonii on the Synergistic Virulence to Human Gingival Epithelial Cells." Frontiers in Cellular and Infection Microbiology 12 (April 29, 2022). http://dx.doi.org/10.3389/fcimb.2022.879423.
Full textAbstract:
In subgingival plaque biofilms, Fusobacterium nucleatum is closely related to the occurrence and development of periodontitis. Streptococcus gordonii, as an accessory pathogen, can coaggregate with periodontal pathogens, facilitating the subgingival colonization of periodontal pathogens. Studies have shown that F. nucleatum can coaggregate with S. gordonii and colonize the subgingival plaque. However, most studies have focused on monocultures or coinfection of species and the potential impact of coaggregation between the two species on periodontal interactions to human gingival epithelial cells (hGECs) remains poorly understood. The present study explored the effect of coaggregation between F. nucleatum and S. gordonii on subgingival synergistic virulence to hGECs. The results showed that coaggregation inhibited the adhesion and invasion of F. nucleatum to hGECs compared with that in the F. nucleatum monoculture and coinfection group. Coaggregation and coinfection with F. nucleatum both enhanced S. gordonii adhesion to hGECs, but neither of the two groups affected S. gordonii invasion to hGECs compared with S. gordonii monoculture. The gene expression levels of TLR2 and TLR4 in hGECs in the coaggregation group were higher than those in the monoculture groups but lower than those in the coinfection group. Compared with coinfection, the coaggregation inhibited apoptosis of hGECs and promoted the secretion of the proinflammatory cytokines TNF-α and IL-6 by hGECs, showed a synergistic inflammatory effect, while coaggregation inhibited the secretion of the anti-inflammatory cytokine TGF-β1. Coaggregation enhanced the phosphorylation of p65, p38, and JNK proteins and therefore activated the NF-κB and MAPK signaling pathways. Pretreatment with a pathway antagonist/inhibitor decreased the phosphorylation levels of proteins and the secretion of TNF-α and IL-6. In conclusion, coaggregation inhibited the adhesion and invasion of F. nucleatum to hGECs. However, it enhanced the adhesion of S. gordonii to hGECs. Compared with coinfection, coaggregation inhibited the apoptosis of hGECs. The coaggregation coordinately promoted the secretion of TNF-α and IL-6 by hGECs through the TLR/NF-κB and TLR/MAPK signaling pathways while inhibiting the secretion of TGF-β1, thus aggravating the inflammatory response of hGECs.
46
Wu, Hongle, Wei Qiu, Xiaofang Zhu, Xiangfen Li, Zhongcong Xie, Isabel Carreras, Alpaslan Dedeoglu, et al. "The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways." Frontiers in Aging Neuroscience 14 (June 23, 2022). http://dx.doi.org/10.3389/fnagi.2022.912709.
Full textAbstract:
Alzheimer’s Disease (AD) is the most common form of dementia in older adults and has a devastating impact on the patient’s quality of life, which creates a significant socio-economic burden for the affected individuals and their families. In recent years, studies have identified a relationship between periodontitis and AD. Periodontitis is an infectious/inflammatory disease that destroys the supporting periodontal structure leading to tooth loss. Dysbiosis of the oral microbiome plays a significant role in the onset and development of periodontitis exhibiting a shift to overgrowth of pathobionts in the normal microflora with increasing local inflammation. Fusobacterium nucleatum is a common pathogen that significantly overgrows in periodontitis and has also been linked to various systemic diseases. Earlier studies have reported that antibodies to F. nucleatum can be detected in the serum of patients with AD or cognitive impairment, but a causal relationship and a plausible mechanism linking the two diseases have not been identified. In this study, we conducted both in vivo and in vitro experiments and found that F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. In our in vivo experiments, we found that F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s symptoms in 5XFAD mice including increased cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the mouse cerebrum. This study may suggest a possible link between a periodontal pathogen and AD and F. nucleatum could be a risk factor in the pathogenesis of AD. We are currently further identifying the pathways through which F. nucleatum modulates molecular elements in enhancing AD symptoms and signs. Data are available via ProteomeXchange with identifier PXD033147.
47
Carda-Diéguez, M., B. T. Rosier, S. Lloret, C. Llena, and A. Mira. "The tongue biofilm metatranscriptome identifies metabolic pathways associated with the presence or absence of halitosis." npj Biofilms and Microbiomes 8, no. 1 (December 19, 2022). http://dx.doi.org/10.1038/s41522-022-00364-2.
Full textAbstract:
AbstractIntra-oral halitosis usually results from the production of volatile sulfur compounds, such as methyl mercaptan and hydrogen sulfide, by the tongue microbiota. There are currently no reports on the microbial gene-expression profiles of the tongue microbiota in halitosis. In this study, we performed RNAseq of tongue coating samples from individuals with and without halitosis. The activity of Streptococcus (including S. parasanguinis), Veillonella (including V. dispar) and Rothia (including R. mucilaginosa) was associated with halitosis-free individuals while Prevotella (including P. shahi), Fusobacterium (including F. nucleatum) and Leptotrichia were associated with halitosis. Interestingly, the metatranscriptome of patients that only had halitosis levels of methyl mercaptan was similar to that of halitosis-free individuals. Finally, gene expression profiles showed a significant over-expression of genes involved in L-cysteine and L-homocysteine synthesis, as well as nitrate reduction genes, in halitosis-free individuals and an over-expression of genes responsible for cysteine degradation into hydrogen sulfide in halitosis patients.
48
Liu, Tingjun, Ruiqi Yang, Jiani Zhou, Xianjun Lu, Zijian Yuan, Xi Wei, and Lihong Guo. "Interactions Between Streptococcus gordonii and Fusobacterium nucleatum Altered Bacterial Transcriptional Profiling and Attenuated the Immune Responses of Macrophages." Frontiers in Cellular and Infection Microbiology 11 (January 7, 2022). http://dx.doi.org/10.3389/fcimb.2021.783323.
Full textAbstract:
Interspecies coaggregation promotes transcriptional changes in oral bacteria, affecting bacterial pathogenicity. Streptococcus gordonii (S. gordonii) and Fusobacterium nucleatum (F. nucleatum) are common oral inhabitants. The present study investigated the transcriptional profiling of S. gordonii and F. nucleatum subsp. polymorphum in response to the dual-species coaggregation using RNA-seq. Macrophages were infected with both species to explore the influence of bacterial coaggregation on both species’ abilities to survive within macrophages and induce inflammatory responses. Results indicated that, after the 30-min dual-species coaggregation, 116 genes were significantly up-regulated, and 151 genes were significantly down-regulated in S. gordonii; 97 genes were significantly down-regulated, and 114 genes were significantly up-regulated in F. nucleatum subsp. polymorphum. Multiple S. gordonii genes were involved in the biosynthesis and export of cell-wall proteins and carbohydrate metabolism. F. nucleatum subsp. polymorphum genes were mostly associated with translation and protein export. The coaggregation led to decreased expression levels of genes associated with lipopolysaccharide and peptidoglycan biosynthesis. Coaggregation between S. gordonii and F. nucleatum subsp. polymorphum significantly promoted both species’ intracellular survival within macrophages and attenuated the production of pro-inflammatory cytokines IL-6 and IL-1β. Physical interactions between these two species promoted a symbiotic lifestyle and repressed macrophage’s killing and pro-inflammatory responses.
49
Yang, Kyung Mi, Ji-Sun Kim, Hye-Sung Kim, Young-Youn Kim, Jeong-Kyu Oh, Hye-Won Jung, Doo-Sang Park, and Kwang-Hak Bae. "Lactobacillus reuteri AN417 cell-free culture supernatant as a novel antibacterial agent targeting oral pathogenic bacteria." Scientific Reports 11, no. 1 (January 15, 2021). http://dx.doi.org/10.1038/s41598-020-80921-x.
Full textAbstract:
AbstractLactobacillus reuteri AN417 is a newly characterized probiotic strain. The activity of AN417 against oral pathogenic bacteria is unknown. We investigated the antibacterial activity of cell-free L. reuteri AN417 culture supernatant (LRS) against three oral pathogens: Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans. P. gingivalis and F. nucleatum have been implicated in periodontal disease, whereas S. mutans causes dental caries. Exposing these oral pathogenic bacteria to LRS significantly reduced their growth rates, intracellular ATP levels, cell viability, and time-to-kill. The minimal inhibitory volume of LRS was 10% (v/v) against P. gingivalis, 20% (v/v) for F. nucleatum, and 30% (v/v) for S. mutans. LRS significantly reduced the integrity of biofilms and significantly suppressed the expression of various genes involved in P. gingivalis biofilm formation. The L. reuteri AN417 genome lacked genes encoding reuterin, reuteran, and reutericyclin, which are major antibacterial compounds produced in L. reuteri strains. LRS treated with lipase and α-amylase displayed decreased antibacterial activity against oral pathogens. These data suggest that the antibacterial substances in LRS are carbohydrates and/or fatty acid metabolites. Our results demonstrate that LRS has antimicrobial activity against dental pathogenic bacteria, highlighting its potential utility for the prevention and treatment of P. gingivalis periodontal disease.
50
Dadashi, Masoud, Bahareh Hajikhani, Ebrahim faghihloo, Parviz Owlia, Somayeh Yaslianifard, Mehdi Goudarzi, Mohammad Javad Nasiri, and Fatemeh fallah. "Proliferative Effect of FadA Recombinant Protein from Fusobacterium nucleatum on SW480 Colorectal Cancer Cell Line." Infectious Disorders - Drug Targets 20 (July 20, 2020). http://dx.doi.org/10.2174/1871526520666200720113004.
Full textAbstract:
Background and Aim: Colorectal Cancer (CRC) is one of the most frequent cancers diagnosed in both men and women worldwide. Fusobacterium nucleatum adhesin A (FadA) has an important potential factor in the development or progression of CRC. The aim of the present study was to evaluate the proliferative effect of recombinant FadA on SW480 colorectal cancer cell line. Materials and Methods: The recombinant pET21(b)-fadA plasmid was synthesized and transformed into competent E.coli DH5α. In the next step, induction and expression of recombinant FadA were carried out in E. coli BL21 (DE3) competent cells. Expression and purification of protein were successfully done and it was analyzed and confirmed by SDS-PAGE and western blotting. The proliferative effect of purified FadA on SW480 CRC cell line was evaluated using MTT assay and cell counting methods. Results: Visualization of the specific band isolated from the linear plasmid on the agarose gel confirmed the presence of the desired gene. After electrophoresis and Coomassie blue staining, the protein of interest with an approximate molecular weight of 13KDa was detected. The MTT assay, similar to cell counting methods, revealed that FadA dose and timedependently promoted SW480 cell growth and proliferation in 24, 48 and 72 hours. Conclusion: The results showed that FadA stimulates proliferation of SW480 colorectal cancer cell line with a dose and time-dependent manner.