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1
Zhang, Mingyue, Yanan Zhou, Xinyuan Cui e Lifeng Zhu. "The Potential of Co-Evolution and Interactions of Gut Bacteria–Phages in Bamboo-Eating Pandas: Insights from Dietary Preference-Based Metagenomic Analysis". Microorganisms 12, n. 4 (31 marzo 2024): 713. http://dx.doi.org/10.3390/microorganisms12040713.
Testo completoAbstract (sommario):
Bacteria and phages are two of the most abundant biological entities in the gut microbiome, and diet and host phylogeny are two of the most critical factors influencing the gut microbiome. A stable gut bacterial community plays a pivotal role in the host’s physiological development and immune health. A phage is a virus that directly infects bacteria, and phages’ close associations and interactions with bacteria are essential for maintaining the stability of the gut bacterial community and the entire microbial ecosystem. Here, we utilized 99 published metagenomic datasets from 38 mammalian species to investigate the relationship (diversity and composition) and potential interactions between gut bacterial and phage communities and the impact of diet and phylogeny on these communities. Our results highlight the co-evolutionary potential of bacterial–phage interactions within the mammalian gut. We observed a higher alpha diversity in gut bacteria than in phages and identified positive correlations between bacterial and phage compositions. Furthermore, our study revealed the significant influence of diet and phylogeny on mammalian gut bacterial and phage communities. We discovered that the impact of dietary factors on these communities was more pronounced than that of phylogenetic factors at the order level. In contrast, phylogenetic characteristics had a more substantial influence at the family level. The similar omnivorous dietary preference and closer phylogenetic relationship (family Ursidae) may contribute to the similarity of gut bacterial and phage communities between captive giant panda populations (GPCD and GPYA) and omnivorous animals (OC; including Sun bear, brown bear, and Asian black bear). This study employed co-occurrence microbial network analysis to reveal the potential interaction patterns between bacteria and phages. Compared to other mammalian groups (carnivores, herbivores, and omnivores), the gut bacterial and phage communities of bamboo-eating species (giant pandas and red pandas) exhibited a higher level of interaction. Additionally, keystone species and modular analysis showed the potential role of phages in driving and maintaining the interaction patterns between bacteria and phages in captive giant pandas. In sum, gaining a comprehensive understanding of the interaction between the gut microbiota and phages in mammals is of great significance, which is of great value in promoting healthy and sustainable mammals and may provide valuable insights into the conservation of wildlife populations, especially endangered animal species.
2
Stone, Edel, Katrina Campbell, Irene Grant e Olivia McAuliffe. "Understanding and Exploiting Phage–Host Interactions". Viruses 11, n. 6 (18 giugno 2019): 567. http://dx.doi.org/10.3390/v11060567.
Testo completoAbstract (sommario):
Initially described a century ago by William Twort and Felix d’Herelle, bacteriophages are bacterial viruses found ubiquitously in nature, located wherever their host cells are present. Translated literally, bacteriophage (phage) means ‘bacteria eater’. Phages interact and infect specific bacteria while not affecting other bacteria or cell lines of other organisms. Due to the specificity of these phage–host interactions, the relationship between phages and their host cells has been the topic of much research. The advances in phage biology research have led to the exploitation of these phage–host interactions and the application of phages in the agricultural and food industry. Phages may provide an alternative to the use of antibiotics, as it is well known that the emergence of antibiotic-resistant bacterial infections has become an epidemic in clinical settings. In agriculture, pre-harvest and/or post-harvest application of phages to crops may prevent the colonisation of bacteria that are detrimental to plant or human health. In addition, the abundance of data generated from genome sequencing has allowed the development of phage-derived bacterial detection systems of foodborne pathogens. This review aims to outline the specific interactions between phages and their host and how these interactions may be exploited and applied in the food industry.
3
Koskella, Britt, e Tiffany B. Taylor. "Multifaceted Impacts of Bacteriophages in the Plant Microbiome". Annual Review of Phytopathology 56, n. 1 (25 agosto 2018): 361–80. http://dx.doi.org/10.1146/annurev-phyto-080417-045858.
Testo completoAbstract (sommario):
Plant-associated bacteria face multiple selection pressures within their environments and have evolved countless adaptations that both depend on and shape bacterial phenotype and their interaction with plant hosts. Explaining bacterial adaptation and evolution therefore requires considering each of these forces independently as well as their interactions. In this review, we examine how bacteriophage viruses (phages) can alter the ecology and evolution of plant-associated bacterial populations and communities. This includes influencing a bacterial population's response to both abiotic and biotic selection pressures and altering ecological interactions within the microbiome and between the bacteria and host plant. We outline specific ways in which phages can alter bacterial phenotype and discuss when and how this might impact plant-microbe interactions, including for plant pathogens. Finally, we highlight key open questions in phage-bacteria-plant research and offer suggestions for future study.
4
Dicks, Leon M. T., e Wian Vermeulen. "Bacteriophage–Host Interactions and the Therapeutic Potential of Bacteriophages". Viruses 16, n. 3 (20 marzo 2024): 478. http://dx.doi.org/10.3390/v16030478.
Testo completoAbstract (sommario):
Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to over-prescribing antibiotics. Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. Enzymes such as endolysins, exolysins, endopeptidases, endosialidases, and depolymerases produced by phages interact with bacterial surfaces, cell wall components, and exopolysaccharides, and may even destroy biofilms. Enzymatic cleavage of the host cell envelope components exposes specific receptors required for phage adhesion. Gram-positive bacteria are susceptible to phage infiltration through their peptidoglycan, cell wall teichoic acid (WTA), lipoteichoic acids (LTAs), and flagella. In Gram-negative bacteria, lipopolysaccharides (LPSs), pili, and capsules serve as targets. Defense mechanisms used by bacteria differ and include physical barriers (e.g., capsules) or endogenous mechanisms such as clustered regularly interspaced palindromic repeat (CRISPR)-associated protein (Cas) systems. Phage proteins stimulate immune responses against specific pathogens and improve antibiotic susceptibility. This review discusses the attachment of phages to bacterial cells, the penetration of bacterial cells, the use of phages in the treatment of bacterial infections, and the limitations of phage therapy. The therapeutic potential of phage-derived proteins and the impact that genomically engineered phages may have in the treatment of infections are summarized.
5
Loessner, Holger, Insea Schlattmeier, Marie Anders-Maurer, Isabelle Bekeredjian-Ding, Christine Rohde, Johannes Wittmann, Cornelia Pokalyuk, Oleg Krut e Christel Kamp. "Kinetic Fingerprinting Links Bacteria-Phage Interactions with Emergent Dynamics: Rapid Depletion of Klebsiella pneumoniae Indicates Phage Synergy". Antibiotics 9, n. 7 (14 luglio 2020): 408. http://dx.doi.org/10.3390/antibiotics9070408.
Testo completoAbstract (sommario):
The specific temporal evolution of bacterial and phage population sizes, in particular bacterial depletion and the emergence of a resistant bacterial population, can be seen as a kinetic fingerprint that depends on the manifold interactions of the specific phage–host pair during the course of infection. We have elaborated such a kinetic fingerprint for a human urinary tract Klebsiella pneumoniae isolate and its phage vB_KpnP_Lessing by a modeling approach based on data from in vitro co-culture. We found a faster depletion of the initially sensitive bacterial population than expected from simple mass action kinetics. A possible explanation for the rapid decline of the bacterial population is a synergistic interaction of phages which can be a favorable feature for phage therapies. In addition to this interaction characteristic, analysis of the kinetic fingerprint of this bacteria and phage combination revealed several relevant aspects of their population dynamics: A reduction of the bacterial concentration can be achieved only at high multiplicity of infection whereas bacterial extinction is hardly accomplished. Furthermore the binding affinity of the phage to bacteria is identified as one of the most crucial parameters for the reduction of the bacterial population size. Thus, kinetic fingerprinting can be used to infer phage–host interactions and to explore emergent dynamics which facilitates a rational design of phage therapies.
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Karlsson, Fredrik, Carl A. K. Borrebaeck, Nina Nilsson e Ann-Christin Malmborg-Hager. "The Mechanism of Bacterial Infection by Filamentous Phages Involves Molecular Interactions between TolA and Phage Protein 3 Domains". Journal of Bacteriology 185, n. 8 (15 aprile 2003): 2628–34. http://dx.doi.org/10.1128/jb.185.8.2628-2634.2003.
Testo completoAbstract (sommario):
ABSTRACT The early events in filamentous bacteriophage infection of gram-negative bacteria are mediated by the gene 3 protein (g3p) of the virus. This protein has a sophisticated domain organization consisting of two N-terminal domains and one C-terminal domain, separated by flexible linkers. The molecular interactions between these domains and the known bacterial coreceptor protein (TolA) were studied using a biosensor technique, and we report here on interactions of the viral coat protein with TolA, as well as on interactions between the TolA molecules. We detected an interaction between the pilus binding second domain (N2) of protein 3 and the bacterial TolA. This novel interaction was found to depend on the periplasmatic domain of TolA (TolAII). Furthermore, extensive interaction was detected between TolA molecules, demonstrating that bacterial TolA has the ability to interact functionally with itself during phage infection. The kinetics of g3p binding to TolA is also different from that of bacteriocins, since both N-terminal domains of g3p were found to interact with TolA. The multiple roles for each of the separate g3p and TolA domains imply a delicate interaction network during the phage infection process and a model for the infection mechanism is hypothesized.
7
Mohammed, Manal, e Beata Orzechowska. "Characterisation of Phage Susceptibility Variation in Salmonellaenterica Serovar Typhimurium DT104 and DT104b". Microorganisms 9, n. 4 (17 aprile 2021): 865. http://dx.doi.org/10.3390/microorganisms9040865.
Testo completoAbstract (sommario):
The surge in mortality and morbidity rates caused by multidrug-resistant (MDR) bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents. Nevertheless, bacteria and phages are continually under the pressure of the evolutionary phage–host arms race for survival, which is mediated by co-evolving resistance mechanisms. In Anderson phage typing scheme of Salmonella Typhimurium, the epidemiologically related definitive phage types, DT104 and DT104b, display significantly different phage susceptibility profiles. This study aimed to characterise phage resistance mechanisms and genomic differences that may be responsible for the divergent phage reaction patterns in S. Typhimurium DT104 and DT104b using whole genome sequencing (WGS). The analysis of intact prophages, restriction–modification systems (RMS), plasmids and clustered regularly interspaced short palindromic repeats (CRISPRs), as well as CRISPR-associated proteins, revealed no unique genetic determinants that might explain the variation in phage susceptibility among the two phage types. Moreover, analysis of genes coding for potential phage receptors revealed no differences among DT104 and DT104b strains. However, the findings propose the need for experimental assessment of phage-specific receptors on the bacterial cell surface and analysis of bacterial transcriptome using RNA sequencing which will explain the differences in bacterial susceptibility to phages. Using Anderson phage typing scheme of Salmonella Typhimurium for the study of bacteria-phage interaction will help improving our understanding of host–phage interactions which will ultimately lead to the development of phage-based technologies, enabling effective infection control.
8
Segundo-Arizmendi, Nallelyt, Dafne Arellano-Maciel, Abraham Rivera-Ramírez, Adán Manuel Piña-González, Gamaliel López-Leal e Efren Hernández-Baltazar. "Bacteriophages: A Challenge for Antimicrobial Therapy". Microorganisms 13, n. 1 (7 gennaio 2025): 100. https://doi.org/10.3390/microorganisms13010100.
Testo completoAbstract (sommario):
Phage therapy, which involves the use of bacteriophages (phages) to combat bacterial infections, is emerging as a promising approach to address the escalating threat posed by multidrug-resistant (MDR) bacteria. This brief review examines the historical background and recent advancements in phage research, focusing on their genomics, interactions with host bacteria, and progress in medical and biotechnological applications. Additionally, we expose key aspects of the mechanisms of action, and therapeutic uses of phage considerations in treating MDR bacterial infections are discussed, particularly in the context of infections related to virus–bacteria interactions.
9
Beckett, Stephen J., e Hywel T. P. Williams. "Coevolutionary diversification creates nested-modular structure in phage–bacteria interaction networks". Interface Focus 3, n. 6 (6 dicembre 2013): 20130033. http://dx.doi.org/10.1098/rsfs.2013.0033.
Testo completoAbstract (sommario):
Phage and their bacterial hosts are the most diverse and abundant biological entities in the oceans, where their interactions have a major impact on marine ecology and ecosystem function. The structure of interaction networks for natural phage–bacteria communities offers insight into their coevolutionary origin. At small phylogenetic scales, observed communities typically show a nested structure, in which both hosts and phages can be ranked by their range of resistance and infectivity, respectively. A qualitatively different multi-scale structure is seen at larger phylogenetic scales; a natural assemblage sampled from the Atlantic Ocean displays large-scale modularity and local nestedness within each module. Here, we show that such ‘nested-modular’ interaction networks can be produced by a simple model of host–phage coevolution in which infection depends on genetic matching. Negative frequency-dependent selection causes diversification of hosts (to escape phages) and phages (to track their evolving hosts). This creates a diverse community of bacteria and phage, maintained by kill-the-winner ecological dynamics. When the resulting communities are visualized as bipartite networks of who infects whom, they show the nested-modular structure characteristic of the Atlantic sample. The statistical significance and strength of this observation varies depending on whether the interaction networks take into account the density of the interacting strains, with implications for interpretation of interaction networks constructed by different methods. Our results suggest that the apparently complex community structures associated with marine bacteria and phage may arise from relatively simple coevolutionary origins.
10
Esteves, Nathaniel C., Danielle N. Bigham e Birgit E. Scharf. "Phages on filaments: A genetic screen elucidates the complex interactions between Salmonella enterica flagellin and bacteriophage Chi". PLOS Pathogens 19, n. 8 (3 agosto 2023): e1011537. http://dx.doi.org/10.1371/journal.ppat.1011537.
Testo completoAbstract (sommario):
The bacterial flagellum is a rotary motor organelle and important virulence factor that propels motile pathogenic bacteria, such as Salmonella enterica, through their surroundings. Bacteriophages, or phages, are viruses that solely infect bacteria. As such, phages have myriad applications in the healthcare field, including phage therapy against antibiotic-resistant bacterial pathogens. Bacteriophage χ (Chi) is a flagellum-dependent (flagellotropic) bacteriophage, which begins its infection cycle by attaching its long tail fiber to the S. enterica flagellar filament as its primary receptor. The interactions between phage and flagellum are poorly understood, as are the reasons that χ only kills certain Salmonella serotypes while others entirely evade phage infection. In this study, we used molecular cloning, targeted mutagenesis, heterologous flagellin expression, and phage-host interaction assays to determine which domains within the flagellar filament protein flagellin mediate this complex interaction. We identified the antigenic N- and C-terminal D2 domains as essential for phage χ binding, with the hypervariable central D3 domain playing a less crucial role. Here, we report that the primary structure of the Salmonella flagellin D2 domains is the major determinant of χ adhesion. The phage susceptibility of a strain is directly tied to these domains. We additionally uncovered important information about flagellar function. The central and most variable domain, D3, is not required for motility in S. Typhimurium 14028s, as it can be deleted or its sequence composition can be significantly altered with minimal impacts on motility. Further knowledge about the complex interactions between flagellotropic phage χ and its primary bacterial receptor may allow genetic engineering of its host range for use as targeted antimicrobial therapy against motile pathogens of the χ-host genera Salmonella, Escherichia, or Serratia.
11
Schiettekatte, Olivier, Elsa Beurrier, Luisa De Sordi e Anne Chevallereau. "“French Phage Network” Annual Conference—Seventh Meeting Report". Viruses 15, n. 2 (10 febbraio 2023): 495. http://dx.doi.org/10.3390/v15020495.
Testo completoAbstract (sommario):
The French Phage Network (Phages.fr) has continuously grown since its foundation, eight years ago. The annual conference, held at the Institut Pasteur in Paris, attracted 164 participants from the 11th to the 13th of October 2022. Researchers from academic laboratories, hospitals and private companies shared their ongoing projects and breakthroughs in the very institute where Felix d’Hérelle developed phage therapy over a century ago. The conference was divided into four thematic sessions, each opened by a keynote lecture: “Interaction between phages, mobile genetic elements and bacterial immune system,” “Ecology and evolution of phage–bacteria interactions,” “Molecular interplay between phages and their hosts” and “Therapeutic and biotechnological applications of phages.” A total of 32 talks and 33 posters were presented during the conference.
12
Koonjan, Shazeeda, Carlos Cardoso Palacios e Anders S. Nilsson. "Population Dynamics of a Two Phages–One Host Infection System Using Escherichia coli Strain ECOR57 and Phages vB_EcoP_SU10 and vB_EcoD_SU57". Pharmaceuticals 15, n. 3 (22 febbraio 2022): 268. http://dx.doi.org/10.3390/ph15030268.
Testo completoAbstract (sommario):
In this study, we looked at the population dynamics of a two phages-one host system using phages vB_EcoP_SU10 (SU10) and vB_EcoD_SU57 (SU57) and the bacteria Escherichia coli, strain ECOR57. Phage-specific growth curves were observed where infections by SU10 resulted in a moderate production of phages and infections by SU57 resulted in a fast and extensive production of phage progeny. Sequentially adding SU10 followed by SU57 did not produce a significant change in growth rates, whereas adding SU57 followed by SU10 resulted in a decrease in SU10 titer The efficiency of the plating assays showed that ECOR57 exhibited a resistance spectrum after infection by both the single and combined phages. Phage-resistant bacteria exhibited four different morphotypes (i.e., normal, slimy, edgy, and pointy). The normal and edgy morphotypes had a high frequency of developing resistance. Bacterial growth and biofilm assays indicated that the edgy and pointy morphotypes reached a stationary phase faster and produced more biofilm compared to the wild type. These findings suggest that the dynamic structure of phage–bacteria communities dictate resistance evolution and development. Understanding when and how resistances arise and phage(s)–hosts interactions could aid in the design of phage therapy treatments.
13
Zhang, Zheng, Fen Yu, Yuanqiang Zou, Ye Qiu, Aiping Wu, Taijiao Jiang e Yousong Peng. "Phage protein receptors have multiple interaction partners and high expressions". Bioinformatics 36, n. 10 (25 febbraio 2020): 2975–79. http://dx.doi.org/10.1093/bioinformatics/btaa123.
Testo completoAbstract (sommario):
Abstract Motivation Receptors on host cells play a critical role in viral infection. How phages select receptors is still unknown. Results Here, we manually curated a high-quality database named phageReceptor, including 427 pairs of phage–host receptor interactions, 341 unique viral species or sub-species and 69 bacterial species. Sugars and proteins were most widely used by phages as receptors. The receptor usage of phages in Gram-positive bacteria was different from that in Gram-negative bacteria. Most protein receptors were located on the outer membrane. The phage protein receptors (PPRs) were highly diverse in their structures, and had little sequence identity and no common protein domain with mammalian virus receptors. Further functional characterization of PPRs in Escherichia coli showed that they had larger node degrees and betweennesses in the protein–protein interaction network, and higher expression levels, than other outer membrane proteins, plasma membrane proteins or other intracellular proteins. These findings were consistent with what observed for mammalian virus receptors reported in previous studies, suggesting that viral protein receptors tend to have multiple interaction partners and high expressions. The study deepens our understanding of virus–host interactions. Availability and implementation phageReceptor is publicly available from: http://www.computationalbiology.cn/phageReceptor/index.html. Supplementary information Supplementary data are available at Bioinformatics online.
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Attrill, Erin L., Rory Claydon, Urszula Łapińska, Mario Recker, Sean Meaden, Aidan T. Brown, Edze R. Westra, Sarah V. Harding e Stefano Pagliara. "Individual bacteria in structured environments rely on phenotypic resistance to phage". PLOS Biology 19, n. 10 (12 ottobre 2021): e3001406. http://dx.doi.org/10.1371/journal.pbio.3001406.
Testo completoAbstract (sommario):
Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria–phage interactions in naturally structured environments.
15
Taslem Mourosi, Jarin, Ayobami Awe, Wenzheng Guo, Himanshu Batra, Harrish Ganesh, Xiaorong Wu e Jingen Zhu. "Understanding Bacteriophage Tail Fiber Interaction with Host Surface Receptor: The Key “Blueprint” for Reprogramming Phage Host Range". International Journal of Molecular Sciences 23, n. 20 (12 ottobre 2022): 12146. http://dx.doi.org/10.3390/ijms232012146.
Testo completoAbstract (sommario):
Bacteriophages (phages), as natural antibacterial agents, are being rediscovered because of the growing threat of multi- and pan-drug-resistant bacterial pathogens globally. However, with an estimated 1031 phages on the planet, finding the right phage to recognize a specific bacterial host is like looking for a needle in a trillion haystacks. The host range of a phage is primarily determined by phage tail fibers (or spikes), which initially mediate reversible and specific recognition and adsorption by susceptible bacteria. Recent significant advances at single-molecule and atomic levels have begun to unravel the structural organization of tail fibers and underlying mechanisms of phage–host interactions. Here, we discuss the molecular mechanisms and models of the tail fibers of the well-characterized T4 phage’s interaction with host surface receptors. Structure–function knowledge of tail fibers will pave the way for reprogramming phage host range and will bring future benefits through more-effective phage therapy in medicine. Furthermore, the design strategies of tail fiber engineering are briefly summarized, including machine-learning-assisted engineering inspired by the increasingly enormous amount of phage genetic information.
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Aishat, A. F., S. B. Manga, I. O. Obaroh, R. J. Bioku e B. Abdulkadir. "An Overview on the Application of Bacteriophage Therapy in Combating Antibiotics Resistance: A Review". UMYU Journal of Microbiology Research (UJMR) 6, n. 1 (30 giugno 2021): 113–19. http://dx.doi.org/10.47430/ujmr.2161.015.
Testo completoAbstract (sommario):
The practice of phage therapy, which uses bacterial viruses (phages) to treat bacterial infections, has been around for almost a century. The universal decline in the effectiveness of antibiotics has generated renewed interest in revisiting this practice. Conventionally, phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Biotechnological advances have further expanded the repertoire of potential phage therapeutics to include novel strategies using bioengineered phages and purified phage lytic proteins. Current research on the use of phages and their lytic proteins, specifically against multidrug resistant bacterial infections, suggests phage therapy has the potential to be used as either an alternative or a supplement to antibiotic treatments. Antibacterial therapies, whether phage- or antibioticbased, have relative advantages and disadvantages accordingly. Many considerations must be taken into account when designing novel therapeutic approaches for preventing and treating bacterial infections. Although much is still unknown about the interactions between phage, bacteria, and human host, the time to take phage therapy seriously seems to be rapidly approaching Keywords: Antibiotic resistance; Antimicrobial; Bacteriophage; Biofilms; Multidrug resistance; Phage; Phage safety; Therapy.
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Ritter, Samantha, Elena T. Wright e Philip Serwer. "Extracellular Interaction of Bacillus thuringiensis, ATP and Phage 0105phi7-2: A Potential New Anti-Bacterial Strategy". Viruses 15, n. 12 (12 dicembre 2023): 2409. http://dx.doi.org/10.3390/v15122409.
Testo completoAbstract (sommario):
The following hypothesis proposes non-diffusive, environmental bacteriophage (phage) motion. (1) Some phage-hosting, motile bacteria undergo chemotaxis down ATP concentration gradients to escape lysis-inducing conditions, such as phage infection. (2) Some phages respond by non-infective binding to the motile bacteria. (3) When the bacteria reach a lower ATP concentration, which is a condition that signals increased density of phage-susceptible bacteria, the phage converts, Trojan-horse-like, to productive binding and infection. This hypothesis was previously proposed for Bacillus thuringiensis siphophage 0105phi7-2. It is tested here and confirmed with the following observations. (1) B. thuringiensis is found, macroscopically, preferentially located at low ATP concentrations when propagated in-gel after inoculation in the center of an artificially generated ATP concentration gradient. (2) Inoculating phage 0105phi7-2 at the bacteria inoculation site, 2–3 h after inoculation of bacteria, results in cell lysing activity that moves with the bacteria, without a visible trail of lysis. Trojan-horse-like behavior is consistent with only biofilm-inhabiting phages because environmental selection for this behavior requires limited fluid flows. We propose using artificial ATP concentration gradients to instigate Trojan-horse-like phage behavior during phage therapy of bacterial biofilms.
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Topka-Bielecka, Gracja, Bożena Nejman-Faleńczyk, Sylwia Bloch, Aleksandra Dydecka, Agnieszka Necel, Alicja Węgrzyn e Grzegorz Węgrzyn. "Phage–Bacteria Interactions in Potential Applications of Bacteriophage vB_EfaS-271 against Enterococcus faecalis". Viruses 13, n. 2 (19 febbraio 2021): 318. http://dx.doi.org/10.3390/v13020318.
Testo completoAbstract (sommario):
Phage therapy is one of main alternative option for antibiotic treatment of bacterial infections, particularly in the era of appearance of pathogenic strains revealing resistance to most or even all known antibiotics. Enterococcus faecalis is one of such pathogens causing serious human infections. In the light of high level of biodiversity of bacteriophages and specificity of phages to bacterial species or even strains, development of effective phage therapy depend, between others, on identification and characterization of a large collection of these viruses, including understanding of their interactions with host bacterial cells. Recently, isolation of molecular characterization of bacteriophage vB_EfaS-271, infecting E. faecalis strains have been reported. In this report, phage–host interactions are reported, including ability of vB_EfaS-271 to infect bacteria forming biofilms, efficiency of eliminating bacterial cells from cultures depending on multiplicity of infection (m.o.i.), toxicity of purified phage particles to mammalian cells, and efficiency of appearance of phage-resistant bacteria. The presented results indicate that vB_EfaS-271 can significantly decrease number of viable E. faecalis cells in biofilms and in liquid cultures and reveals no considerable toxicity to mammalian cells. Efficiency of formation of phage-resistant bacteria was dependent on m.o.i. and was higher when the virion-cell ratio was as high as 10 than at low (between 0.01 and 0.0001) m.o.i. values. We conclude that vB_EfaS-271 may be considered as a candidate for its further use in phage therapy.
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Song, Jiaoyang, Zhengjie Liu, Qing Zhang, Yuqing Liu e Yibao Chen. "Phage Engineering for Targeted Multidrug-Resistant Escherichia coli". International Journal of Molecular Sciences 24, n. 3 (27 gennaio 2023): 2459. http://dx.doi.org/10.3390/ijms24032459.
Testo completoAbstract (sommario):
The lytic bacteriophages have potential application value in the treatment of bacterial infections. However, the narrow host spectrum of these phages limits their range of clinical application. Here, we demonstrate the use of scarless Cas9-assisted recombination (no-SCAR) gene-editing technology to regulate phage–host range. We used phage PHB20 as the scaffold to create agents targeting different multidrug-resistant Escherichia coli by replacing its phage tail fiber gene (ORF40). The engineered phages were polyvalent and capable of infecting both the original host bacteria and new targets. Phage-tail fiber genes can be amplified by PCR to construct a recombinant phage PHB20 library that can deal with multidrug-resistant bacteria in the future. Our results provide a better understanding of phage–host interactions, and we describe new anti-bacterial editing methods.
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Van Belleghem, Jonas, Krystyna Dąbrowska, Mario Vaneechoutte, Jeremy Barr e Paul Bollyky. "Interactions between Bacteriophage, Bacteria, and the Mammalian Immune System". Viruses 11, n. 1 (25 dicembre 2018): 10. http://dx.doi.org/10.3390/v11010010.
Testo completoAbstract (sommario):
The human body is host to large numbers of bacteriophages (phages)–a diverse group of bacterial viruses that infect bacteria. Phage were previously regarded as bystanders that only impacted immunity indirectly via effects on the mammalian microbiome. However, it has become clear that phages also impact immunity directly, in ways that are typically anti-inflammatory. Phages can modulate innate immunity via phagocytosis and cytokine responses, but also impact adaptive immunity via effects on antibody production and effector polarization. Phages may thereby have profound effects on the outcome of bacterial infections by modulating the immune response. In this review we highlight the diverse ways in which phages interact with human cells. We present a computational model for predicting these complex and dynamic interactions. These models predict that the phageome may play important roles in shaping mammalian-bacterial interactions.
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Mi, Yanze, Yile He, Jinhui Mi, Yunfei Huang, Huahao Fan, Lihua Song, Xiaoping An, Shan Xu, Mengzhe Li e Yigang Tong. "Genetic and Phenotypic Analysis of Phage-Resistant Mutant Fitness Triggered by Phage–Host Interactions". International Journal of Molecular Sciences 24, n. 21 (26 ottobre 2023): 15594. http://dx.doi.org/10.3390/ijms242115594.
Testo completoAbstract (sommario):
The emergence of phage-resistant bacterial strains is one of the biggest challenges for phage therapy. However, the emerging phage-resistant bacteria are often accompanied by adaptive trade-offs, which supports a therapeutic strategy called “phage steering”. The key to phage steering is to guide the bacterial population toward an evolutionary direction that is favorable for treatment. Thus, it is important to systematically investigate the impacts of phages targeting different bacterial receptors on the fitness of the bacterial population. Herein, we employed 20 different phages to impose strong evolutionary pressure on the host Pseudomonas aeruginosa PAO1 and examined the genetic and phenotypic responses of their phage-resistant mutants. Among these strains with impaired adsorptions, four types of mutations associated with bacterial receptors were identified, namely, lipopolysaccharides (LPSs), type IV pili (T4Ps), outer membrane proteins (OMPs), and exopolysaccharides (EPSs). PAO1, responding to LPS- and EPS-dependent phage infections, mostly showed significant growth impairment and virulence attenuation. Most mutants with T4P-related mutations exhibited a significant decrease in motility and biofilm formation ability, while the mutants with OMP-related mutations required the lowest fitness cost out of the bacterial populations. Apart from fitness costs, PAO1 strains might lose their resistance to antibiotics when counteracting with phages, such as the presence of large-fragment mutants in this study, which may inspire the usage of phage–antibiotic combination strategies. This work provides methods that leverage the merits of phage resistance relative to obtaining therapeutically beneficial outcomes with respect to phage-steering strategies.
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Gummalla, Vimathi S., Yujie Zhang, Yen-Te Liao e Vivian C. H. Wu. "The Role of Temperate Phages in Bacterial Pathogenicity". Microorganisms 11, n. 3 (21 febbraio 2023): 541. http://dx.doi.org/10.3390/microorganisms11030541.
Testo completoAbstract (sommario):
Bacteriophages are viruses that infect bacteria and archaea and are classified as virulent or temperate phages based on their life cycles. A temperate phage, also known as a lysogenic phage, integrates its genomes into host bacterial chromosomes as a prophage. Previous studies have indicated that temperate phages are beneficial to their susceptible bacterial hosts by introducing additional genes to bacterial chromosomes, creating a mutually beneficial relationship. This article reviewed three primary ways temperate phages contribute to the bacterial pathogenicity of foodborne pathogens, including phage-mediated virulence gene transfer, antibiotic resistance gene mobilization, and biofilm formation. This study provides insights into mechanisms of phage–bacterium interactions in the context of foodborne pathogens and provokes new considerations for further research to avoid the potential of phage-mediated harmful gene transfer in agricultural environments.
23
Makalatia, Khatuna, Elene Kakabadze, Nata Bakuradze, Nino Grdzelishvili, Ben Stamp, Ezra Herman, Avraam Tapinos et al. "Investigation of Salmonella Phage–Bacteria Infection Profiles: Network Structure Reveals a Gradient of Target-Range from Generalist to Specialist Phage Clones in Nested Subsets". Viruses 13, n. 7 (28 giugno 2021): 1261. http://dx.doi.org/10.3390/v13071261.
Testo completoAbstract (sommario):
Bacteriophages that lyse Salmonella enterica are potential tools to target and control Salmonella infections. Investigating the host range of Salmonella phages is a key to understand their impact on bacterial ecology, coevolution and inform their use in intervention strategies. Virus–host infection networks have been used to characterize the “predator–prey” interactions between phages and bacteria and provide insights into host range and specificity. Here, we characterize the target-range and infection profiles of 13 Salmonella phage clones against a diverse set of 141 Salmonella strains. The environmental source and taxonomy contributed to the observed infection profiles, and genetically proximal phages shared similar infection profiles. Using in vitro infection data, we analyzed the structure of the Salmonella phage–bacteria infection network. The network has a non-random nested organization and weak modularity suggesting a gradient of target-range from generalist to specialist species with nested subsets, which are also observed within and across the different phage infection profile groups. Our results have implications for our understanding of the coevolutionary mechanisms shaping the ecological interactions between Salmonella phages and their bacterial hosts and can inform strategies for targeting Salmonella enterica with specific phage preparations.
24
Li, Xiang-Yi, Tim Lachnit, Sebastian Fraune, Thomas C. G. Bosch, Arne Traulsen e Michael Sieber. "Temperate phages as self-replicating weapons in bacterial competition". Journal of The Royal Society Interface 14, n. 137 (dicembre 2017): 20170563. http://dx.doi.org/10.1098/rsif.2017.0563.
Testo completoAbstract (sommario):
Microbial communities are accompanied by a diverse array of viruses. Through infections of abundant microbes, these viruses have the potential to mediate competition within the community, effectively weakening competitive interactions and promoting coexistence. This is of particular relevance for host-associated microbial communities, because the diversity of the microbiota has been linked to host health and functioning. Here, we study the interaction between two key members of the microbiota of the freshwater metazoan Hydra vulgaris . The two commensal bacteria Curvibacter sp. and Duganella sp. protect their host from fungal infections, but only if both of them are present. Coexistence of the two bacteria is thus beneficial for Hydra . Intriguingly, Duganella sp. appears to be the superior competitor in vitro due to its higher growth rate when both bacteria are grown separately, but in co-culture the outcome of competition depends on the relative initial abundances of the two species. The presence of an inducible prophage in the Curvibacter sp. genome, which is able to lytically infect Duganella sp., led us to hypothesize that the phage modulates the interaction between these two key members of the Hydra microbiota. Using a mathematical model, we show that the interplay of the lysogenic life cycle of the Curvibacter phage and the lytic life cycle on Duganella sp. can explain the observed complex competitive interaction between the two bacteria. Our results highlight the importance of taking lysogeny into account for understanding microbe–virus interactions and show the complex role phages can play in promoting coexistence of their bacterial hosts.
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Hibstu, Zigale. "Phage Therapy: A Different Approach to Fight Bacterial Infections". Journal of Clinical Case Reports & Studies 4, n. 4 (26 maggio 2023): 01–11. http://dx.doi.org/10.31579/2690-8808/168.
Testo completoAbstract (sommario):
Phage therapy is one of the alternatives to treat infections caused by both antibiotic sensitive and resistant bacteria with no or low toxicity to patients. It was started a century back although rapidly growing bacterial antimicrobial resistance impacting large morbidity, mortality, and financial cost initiated the revival of it. It involves the use of live lytic, bio-engineered, phage-encoded biological products and in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body after seven days of clearing infection. They target specific bacterial strains and cause minimal disruption of microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying high phage titer for therapy exposes them and activates the host immune system. Up to date, no serious side effects are reported with phage human therapy. In this review, we narrated phage - phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, therapeutic application of modified phages and phage-encoded products. We also highlighted the comparison of antibiotics and lytic phage therapy, pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling and current challenges in phage therapy.
26
Carroll-Portillo, Amanda, e Henry C. Lin. "Exploring Mucin as Adjunct to Phage Therapy". Microorganisms 9, n. 3 (28 febbraio 2021): 509. http://dx.doi.org/10.3390/microorganisms9030509.
Testo completoAbstract (sommario):
Conventional phage therapy using bacteriophages (phages) for specific targeting of pathogenic bacteria is not always useful as a therapeutic for gastrointestinal (GI) dysfunction. Complex dysbiotic GI disorders such as small intestinal bowel overgrowth (SIBO), ulcerative colitis (UC), or Crohn’s disease (CD) are even more difficult to treat as these conditions have shifts in multiple populations of bacteria within the microbiome. Such community-level structural changes in the gut microbiota may require an alternative to conventional phage therapy such as fecal virome transfer or a phage cocktail capable of targeting multiple bacterial species. Additionally, manipulation of the GI microenvironment may enhance beneficial bacteria–phage interactions during treatment. Mucin, produced along the entire length of the GI tract to protect the underlying mucosa, is a prominent contributor to the GI microenvironment and may facilitate bacteria–phage interactions in multiple ways, potentially serving as an adjunct during phage therapy. In this review, we will describe what is known about the role of mucin within the GI tract and how its facilitation of bacteria–phage interactions should be considered in any effort directed at optimizing effectiveness of a phage therapy for gastrointestinal dysbiosis.
27
Vasse, Marie, e Sébastien Wielgoss. "Bacteriophages of Myxococcus xanthus, a Social Bacterium". Viruses 10, n. 7 (18 luglio 2018): 374. http://dx.doi.org/10.3390/v10070374.
Testo completoAbstract (sommario):
Bacteriophages have been used as molecular tools in fundamental biology investigations for decades. Beyond this, however, they play a crucial role in the eco-evolutionary dynamics of bacterial communities through their demographic impact and the source of genetic information they represent. The increasing interest in describing ecological and evolutionary aspects of bacteria–phage interactions has led to major insights into their fundamental characteristics, including arms race dynamics and acquired bacterial immunity. Here, we review knowledge on the phages of the myxobacteria with a major focus on phages infecting Myxococcus xanthus, a bacterial model system widely used to study developmental biology and social evolution. In particular, we focus upon the isolation of myxophages from natural sources and describe the morphology and life cycle parameters, as well as the molecular genetics and genomics of the major groups of myxophages. Finally, we propose several interesting research directions which focus on the interplay between myxobacterial host sociality and bacteria–phage interactions.
28
Bucher, Michael J., e Daniel M. Czyż. "Phage against the Machine: The SIE-ence of Superinfection Exclusion". Viruses 16, n. 9 (23 agosto 2024): 1348. http://dx.doi.org/10.3390/v16091348.
Testo completoAbstract (sommario):
Prophages can alter their bacterial hosts to prevent other phages from infecting the same cell, a mechanism known as superinfection exclusion (SIE). Such alterations are facilitated by phage interactions with critical bacterial components involved in motility, adhesion, biofilm production, conjugation, antimicrobial resistance, and immune evasion. Therefore, the impact of SIE extends beyond the immediate defense against superinfection, influencing the overall fitness and virulence of the bacteria. Evaluating the interactions between phages and their bacterial targets is critical for leading phage therapy candidates like Pseudomonas aeruginosa, a Gram-negative bacterium responsible for persistent and antibiotic-resistant opportunistic infections. However, comprehensive literature on the mechanisms underlying SIE remains scarce. Here, we provide a compilation of well-characterized and potential mechanisms employed by Pseudomonas phages to establish SIE. We hypothesize that the fitness costs imposed by SIE affect bacterial virulence, highlighting the potential role of this mechanism in the management of bacterial infections.
29
Nilsson, Emelie, Oliver W. Bayfield, Daniel Lundin, Alfred A. Antson e Karin Holmfeldt. "Diversity and Host Interactions among Virulent and Temperate Baltic Sea Flavobacterium Phages". Viruses 12, n. 2 (30 gennaio 2020): 158. http://dx.doi.org/10.3390/v12020158.
Testo completoAbstract (sommario):
Viruses in aquatic environments play a key role in microbial population dynamics and nutrient cycling. In particular, bacteria of the phylum Bacteriodetes are known to participate in recycling algal blooms. Studies of phage–host interactions involving this phylum are hence important to understand the processes shaping bacterial and viral communities in the ocean as well as nutrient cycling. In this study, we isolated and sequenced three strains of flavobacteria—LMO6, LMO9, LMO8—and 38 virulent phages infecting them. These phages represent 15 species, occupying three novel genera. Additionally, one temperate phage was induced from LMO6 and was found to be competent at infecting LMO9. Functions could be predicted for a limited number of phage genes, mainly representing roles in DNA replication and virus particle formation. No metabolic genes were detected. While the phages isolated on LMO8 could infect all three bacterial strains, the LMO6 and LMO9 phages could not infect LMO8. Of the phages isolated on LMO9, several showed a host-derived reduced efficiency of plating on LMO6, potentially due to differences in DNA methyltransferase genes. Overall, these phage–host systems contribute novel genetic information to our sequence databases and present valuable tools for the study of both virulent and temperate phages.
30
de Sousa, Jorge A. M., Amandine Buffet, Matthieu Haudiquet, Eduardo P. C. Rocha e Olaya Rendueles. "Modular prophage interactions driven by capsule serotype select for capsule loss under phage predation". ISME Journal 14, n. 12 (30 luglio 2020): 2980–96. http://dx.doi.org/10.1038/s41396-020-0726-z.
Testo completoAbstract (sommario):
Abstract Klebsiella species are able to colonize a wide range of environments and include worrisome nosocomial pathogens. Here, we sought to determine the abundance and infectivity of prophages of Klebsiella to understand how the interactions between induced prophages and bacteria affect population dynamics and evolution. We identified many prophages in the species, placing these taxa among the top 5% of the most polylysogenic bacteria. We selected 35 representative strains of the Klebsiella pneumoniae species complex to establish a network of induced phage–bacteria interactions. This revealed that many prophages are able to enter the lytic cycle, and subsequently kill or lysogenize closely related Klebsiella strains. Although 60% of the tested strains could produce phages that infect at least one other strain, the interaction network of all pairwise cross-infections is very sparse and mostly organized in modules corresponding to the strains’ capsule serotypes. Accordingly, capsule mutants remain uninfected showing that the capsule is a key factor for successful infections. Surprisingly, experiments in which bacteria are predated by their own prophages result in accelerated loss of the capsule. Our results show that phage infectiousness defines interaction modules between small subsets of phages and bacteria in function of capsule serotype. This limits the role of prophages as competitive weapons because they can infect very few strains of the species complex. This should also restrict phage-driven gene flow across the species. Finally, the accelerated loss of the capsule in bacteria being predated by their own phages, suggests that phages drive serotype switch in nature.
31
Abedon, Stephen T. "How Simple Maths Can Inform Our Basic Understanding of Phage Therapy". Clinical Infectious Diseases 77, Supplement_5 (1 novembre 2023): S401—S406. http://dx.doi.org/10.1093/cid/ciad480.
Testo completoAbstract (sommario):
Abstract Phage therapy is the application of bacterial viruses to control and, ideally, to eliminate problematic bacteria from patients. Usually employed are so-called strictly lytic phages, which upon adsorption of a bacterium should give rise to both bacterial death and bacterial lysis. This killing occurs with single-hit kinetics, resulting in relatively simple ways to mathematically model organismal-level, phage-bacterium interactions. Reviewed here are processes of phage therapy as viewed from these simpler mathematical perspectives, starting with phage dosing, continuing through phage adsorption of bacteria, and then considering the potential for phage numbers to be enhanced through in situ phage population growth. Overall, I suggest that a basic working knowledge of the underlying “simple maths” of phage therapy can be helpful toward making dosing decisions and predicting certain outcomes. This especially is during controlled in vitro experimentation but is relevant to thinking about in vivo applications as well.
32
Carroll-Portillo, Amanda, Kellin N. Rumsey, Cody A. Braun, Derek M. Lin, Cristina N. Coffman, Joe A. Alcock, Sudha B. Singh e Henry C. Lin. "Mucin and Agitation Shape Predation of Escherichia coli by Lytic Coliphage". Microorganisms 11, n. 2 (17 febbraio 2023): 508. http://dx.doi.org/10.3390/microorganisms11020508.
Testo completoAbstract (sommario):
The ability of bacteriophage (phage), abundant within the gastrointestinal microbiome, to regulate bacterial populations within the same micro-environment offers prophylactic and therapeutic opportunities. Bacteria and phage have both been shown to interact intimately with mucin, and these interactions invariably effect the outcomes of phage predation within the intestine. To better understand the influence of the gastrointestinal micro-environment on phage predation, we employed enclosed, in vitro systems to investigate the roles of mucin concentration and agitation as a function of phage type and number on bacterial killing. Using two lytic coliphage, T4 and PhiX174, bacterial viability was quantified following exposure to phages at different multiplicities of infection (MOI) within increasing, physiological levels of mucin (0–4%) with and without agitation. Comparison of bacterial viability outcomes demonstrated that at low MOI, agitation in combination with higher mucin concentration (>2%) inhibited phage predation by both phages. However, when MOI was increased, PhiX predation was recovered regardless of mucin concentration or agitation. In contrast, only constant agitation of samples containing a high MOI of T4 demonstrated phage predation; briefly agitated samples remained hindered. Our results demonstrate that each phage–bacteria pairing is uniquely influenced by environmental factors, and these should be considered when determining the potential efficacy of phage predation under homeostatic or therapeutic circumstances.
33
Bonilla-Rosso, Germán, Théodora Steiner, Fabienne Wichmann, Evan Bexkens e Philipp Engel. "Honey bees harbor a diverse gut virome engaging in nested strain-level interactions with the microbiota". Proceedings of the National Academy of Sciences 117, n. 13 (16 marzo 2020): 7355–62. http://dx.doi.org/10.1073/pnas.2000228117.
Testo completoAbstract (sommario):
The honey bee gut microbiota influences bee health and has become an important model to study the ecology and evolution of microbiota–host interactions. Yet, little is known about the phage community associated with the bee gut, despite its potential to modulate bacterial diversity or to govern important symbiotic functions. Here we analyzed two metagenomes derived from virus-like particles, analyzed the prevalence of the identified phages across 73 bacterial metagenomes from individual bees, and tested the host range of isolated phages. Our results show that the honey bee gut virome is composed of at least 118 distinct clusters corresponding to both temperate and lytic phages and representing novel genera with a large repertoire of unknown gene functions. We find that the phage community is prevalent in honey bees across space and time and targets the core members of the bee gut microbiota. The large number and high genetic diversity of the viral clusters seems to mirror the high extent of strain-level diversity in the bee gut microbiota. We isolated eight lytic phages that target the core microbiota member Bifidobacterium asteroides, but that exhibited different host ranges at the strain level, resulting in a nested interaction network of coexisting phages and bacterial strains. Collectively, our results show that the honey bee gut virome consists of a complex and diverse phage community that likely plays an important role in regulating strain-level diversity in the bee gut and that holds promise as an experimental model to study bacteria–phage dynamics in natural microbial communities.
34
Abedon, Stephen T., Katarzyna M. Danis-Wlodarczyk, Daniel J. Wozniak e Matthew B. Sullivan. "Improving Phage-Biofilm In Vitro Experimentation". Viruses 13, n. 6 (19 giugno 2021): 1175. http://dx.doi.org/10.3390/v13061175.
Testo completoAbstract (sommario):
Bacteriophages or phages, the viruses of bacteria, are abundant components of most ecosystems, including those where bacteria predominantly occupy biofilm niches. Understanding the phage impact on bacterial biofilms therefore can be crucial toward understanding both phage and bacterial ecology. Here, we take a critical look at the study of bacteriophage interactions with bacterial biofilms as carried out in vitro, since these studies serve as bases of our ecological and therapeutic understanding of phage impacts on biofilms. We suggest that phage-biofilm in vitro experiments often may be improved in terms of both design and interpretation. Specific issues discussed include (a) not distinguishing control of new biofilm growth from removal of existing biofilm, (b) inadequate descriptions of phage titers, (c) artificially small overlying fluid volumes, (d) limited explorations of treatment dosing and duration, (e) only end-point rather than kinetic analyses, (f) importance of distinguishing phage enzymatic from phage bacteriolytic anti-biofilm activities, (g) limitations of biofilm biomass determinations, (h) free-phage interference with viable-count determinations, and (i) importance of experimental conditions. Toward bettering understanding of the ecology of bacteriophage-biofilm interactions, and of phage-mediated biofilm disruption, we discuss here these various issues as well as provide tips toward improving experiments and their reporting.
35
Koskella, Britt, e Nicole Parr. "The evolution of bacterial resistance against bacteriophages in the horse chestnut phyllosphere is general across both space and time". Philosophical Transactions of the Royal Society B: Biological Sciences 370, n. 1675 (19 agosto 2015): 20140297. http://dx.doi.org/10.1098/rstb.2014.0297.
Testo completoAbstract (sommario):
Insight to the spatial and temporal scales of coevolution is key to predicting the outcome of host–parasite interactions and spread of disease. For bacteria infecting long-lived hosts, selection to overcome host defences is just one factor shaping the course of evolution; populations will also be competing with other microbial species and will themselves be facing infection by bacteriophage viruses. Here, we examine the temporal and spatial patterns of bacterial adaptation against natural phage populations from within leaves of horse chestnut trees. Using a time-shift experiment with both sympatric and allopatric phages from either contemporary or earlier points in the season, we demonstrate that bacterial resistance is higher against phages from the past, regardless of spatial sympatry or how much earlier in the season phages were collected. Similarly, we show that future bacterial hosts are more resistant to both sympatric and allopatric phages than contemporary bacterial hosts. Together, our results suggest the evolution of relatively general bacterial resistance against phages in nature and are contrasting to previously observed patterns of phage adaptation to bacteria from the same tree hosts over the same time frame, indicating a potential asymmetry in coevolutionary dynamics.
36
Kim, Kang Eun, Hyoung Min Joo, Yu Jin Kim, Donhyug Kang, Taek-Kyun Lee, Seung Won Jung e Sun-Yong Ha. "Ecological Interaction between Bacteriophages and Bacteria in Sub-Arctic Kongsfjorden Bay, Svalbard, Norway". Microorganisms 12, n. 2 (28 gennaio 2024): 276. http://dx.doi.org/10.3390/microorganisms12020276.
Testo completoAbstract (sommario):
Marine virus diversity and their relationships with their hosts in the marine environment remain unclear. This study investigated the co-occurrence of marine DNA bacteriophages (phages) and bacteria in the sub-Arctic area of Kongsfjorden Bay in Svalbard (Norway) in April and June 2018 using metagenomics tools. Of the marine viruses identified, 48–81% were bacteriophages of the families Myoviridae, Siphoviridae, and Podoviridae. Puniceispirillum phage HMO-2011 was dominant (7.61%) in April, and Puniceispirillum phage HMO-2011 (3.32%) and Pelagibacter phage HTVC008M (3.28%) were dominant in June. Gammaproteobacteria (58%), including Eionea flava (14.3%) and Pseudomonas sabulinigri (12.2%), were dominant in April, whereas Alphaproteobacteria (87%), including Sulfitobacter profundi (51.5%) and Loktanella acticola (32.4%), were dominant in June. The alpha diversity of the bacteriophages and bacterial communities exhibited opposite patterns. The diversity of the bacterial community was higher in April and lower in June. Changes in water temperature and light can influence the relationship between bacteria and bacteriophages.
37
Yerushalmy, Ortal, Ron Braunstein, Sivan Alkalay-Oren, Amit Rimon, Shunit Coppenhagn-Glazer, Hadil Onallah, Ran Nir-Paz e Ronen Hazan. "Towards Standardization of Phage Susceptibility Testing: The Israeli Phage Therapy Center “Clinical Phage Microbiology”—A Pipeline Proposal". Clinical Infectious Diseases 77, Supplement_5 (1 novembre 2023): S337—S351. http://dx.doi.org/10.1093/cid/ciad514.
Testo completoAbstract (sommario):
Abstract Using phages as salvage therapy for nonhealing infections is gaining recognition as a viable solution for patients with such infections. The escalating issue of antibiotic resistance further emphasizes the significance of using phages in treating bacterial infections, encompassing compassionate-use scenarios and clinical trials. Given the high specificity of phages, selecting the suitable phage(s) targeting the causative bacteria becomes critical for achieving treatment success. However, in contrast to conventional antibiotics, where susceptibility-testing procedures were well established for phage therapy, there is a lack of standard frameworks for matching phages from a panel to target bacterial strains and assessing their interactions with antibiotics or other agents. This review discusses and compares published methods for clinical phage microbiology, also known as phage susceptibility testing, and proposes guidelines for establishing a standard pipeline based on our findings over the past 5 years of phage therapy at the Israeli Phage Therapy Center.
38
Tesfaigzi, Johannes, e Roland Süssmuth. "Proportion of phage-insensitive and phage-sensitive cells within pure strains of lactic streptococci, and the influence of calcium". Journal of Dairy Research 56, n. 1 (febbraio 1989): 151–54. http://dx.doi.org/10.1017/s0022029900026327.
Testo completoAbstract (sommario):
It is of industrial importance to investigate the interaction ofStreptococcus lactiswith phages. Although it has been long recognized that in phage–bacterial relationships the phage-carrier state can occur (Hunter, 1947), relatively little study has been done on this subject. The terras ‘phage-carrier state’ and ‘pseudolysogeny’ have been used synonymously to describe bacterial cultures which are persistently infected with a virus (Barksdale & Arden, 1974, Lawrenceet al.1976). The phagecarrier state differs from lysogenesis in that the bacteria are easily separated from the bacteriophage by a simple plating and re-isolation procedure (Grahamet al.1952). Süssmuth & Tayran (1986) showed that after lysis of one single strain, phage and phage-insensitive bacteria coexist. This work investigates the proportion of phage-insensitive bacteria remaining after lysis of otherStr. lactisstrains, the effect of calcium on this proportion, and the number of generations required to return to a normal sensitive population.
39
Maffei, Enea, Aisylu Shaidullina, Marco Burkolter, Yannik Heyer, Fabienne Estermann, Valentin Druelle, Patrick Sauer et al. "Systematic exploration of Escherichia coli phage–host interactions with the BASEL phage collection". PLOS Biology 19, n. 11 (16 novembre 2021): e3001424. http://dx.doi.org/10.1371/journal.pbio.3001424.
Testo completoAbstract (sommario):
Bacteriophages, the viruses infecting bacteria, hold great potential for the treatment of multidrug-resistant bacterial infections and other applications due to their unparalleled diversity and recent breakthroughs in their genetic engineering. However, fundamental knowledge of the molecular mechanisms underlying phage–host interactions is mostly confined to a few traditional model systems and did not keep pace with the recent massive expansion of the field. The true potential of molecular biology encoded by these viruses has therefore remained largely untapped, and phages for therapy or other applications are often still selected empirically. We therefore sought to promote a systematic exploration of phage–host interactions by composing a well-assorted library of 68 newly isolated phages infecting the model organism Escherichia coli that we share with the community as the BASEL (BActeriophage SElection for your Laboratory) collection. This collection is largely representative of natural E. coli phage diversity and was intensively characterized phenotypically and genomically alongside 10 well-studied traditional model phages. We experimentally determined essential host receptors of all phages, quantified their sensitivity to 11 defense systems across different layers of bacterial immunity, and matched these results to the phages’ host range across a panel of pathogenic enterobacterial strains. Clear patterns in the distribution of phage phenotypes and genomic features highlighted systematic differences in the potency of different immunity systems and suggested the molecular basis of receptor specificity in several phage groups. Our results also indicate strong trade-offs between fitness traits like broad host recognition and resistance to bacterial immunity that might drive the divergent adaptation of different phage groups to specific ecological niches. We envision that the BASEL collection will inspire future work exploring the biology of bacteriophages and their hosts by facilitating the discovery of underlying molecular mechanisms as the basis for an effective translation into biotechnology or therapeutic applications.
40
Donati, Valentina L., Inger Dalsgaard, Anniina Runtuvuori-Salmela, Heidi Kunttu, Johanna Jørgensen, Daniel Castillo, Lotta-Riina Sundberg, Mathias Middelboe e Lone Madsen. "Interactions between Rainbow Trout Eyed Eggs and Flavobacterium spp. Using a Bath Challenge Model: Preliminary Evaluation of Bacteriophages as Pathogen Control Agents". Microorganisms 9, n. 5 (30 aprile 2021): 971. http://dx.doi.org/10.3390/microorganisms9050971.
Testo completoAbstract (sommario):
The microbial community surrounding fish eyed eggs can harbor pathogenic bacteria. In this study we focused on rainbow trout (Oncorhynchus mykiss) eyed eggs and the potential of bacteriophages against the pathogenic bacteria Flavobacterium psychrophilum and F. columnare. An infection bath method was first established, and the effects of singular phages on fish eggs was assessed (survival of eyed eggs, interaction of phages with eyed eggs). Subsequently, bacteria-challenged eyed eggs were exposed to phages to evaluate their effects in controlling the bacterial population. Culture-based methods were used to enumerate the number of bacteria and/or phages associated with eyed eggs and in the surrounding environment. The results of the study showed that, with our infection model, it was possible to re-isolate F. psychrophilum associated with eyed eggs after the infection procedure, without affecting the survival of the eggs in the short term. However, this was not possible for F. columnare, as this bacterium grows at higher temperatures than the ones recommended for incubation of rainbow trout eyed eggs. Bacteriophages do not appear to negatively affect the survival of rainbow trout eyed eggs and they do not seem to strongly adhere to the surface of eyed eggs either. Finally, the results demonstrated a strong potential for short term (24 h) phage control of F. psychrophilum. However, further studies are needed to explore if phage control can be maintained for a longer period and to further elucidate the mechanisms of interactions between Flavobacteria and their phages in association with fish eggs.
41
Bulssico, Julián, Irina PapukashvilI, Leon Espinosa, Sylvain Gandon e Mireille Ansaldi. "Phage-antibiotic synergy: Cell filamentation is a key driver of successful phage predation". PLOS Pathogens 19, n. 9 (13 settembre 2023): e1011602. http://dx.doi.org/10.1371/journal.ppat.1011602.
Testo completoAbstract (sommario):
Phages are promising tools to fight antibiotic-resistant bacteria, and as for now, phage therapy is essentially performed in combination with antibiotics. Interestingly, combined treatments including phages and a wide range of antibiotics lead to an increased bacterial killing, a phenomenon called phage-antibiotic synergy (PAS), suggesting that antibiotic-induced changes in bacterial physiology alter the dynamics of phage propagation. Using single-phage and single-cell techniques, each step of the lytic cycle of phage HK620 was studied in E. coli cultures treated with either ceftazidime, cephalexin or ciprofloxacin, three filamentation-inducing antibiotics. In the presence of sublethal doses of antibiotics, multiple stress tolerance and DNA repair pathways are triggered following activation of the SOS response. One of the most notable effects is the inhibition of bacterial division. As a result, a significant fraction of cells forms filaments that stop dividing but have higher rates of mutagenesis. Antibiotic-induced filaments become easy targets for phages due to their enlarged surface areas, as demonstrated by fluorescence microscopy and flow cytometry techniques. Adsorption, infection and lysis occur more often in filamentous cells compared to regular-sized bacteria. In addition, the reduction in bacterial numbers caused by impaired cell division may account for the faster elimination of bacteria during PAS. We developed a mathematical model to capture the interaction between sublethal doses of antibiotics and exposition to phages. This model shows that the induction of filamentation by sublethal doses of antibiotics can amplify the replication of phages and therefore yield PAS. We also use this model to study the consequences of PAS on the emergence of antibiotic resistance. A significant percentage of hyper-mutagenic filamentous bacteria are effectively killed by phages due to their increased susceptibility to infection. As a result, the addition of even a very low number of bacteriophages produced a strong reduction of the mutagenesis rate of the entire bacterial population. We confirm this prediction experimentally using reporters for bacterial DNA repair. Our work highlights the multiple benefits associated with the combination of sublethal doses of antibiotics with bacteriophages.
42
Kraus, Samuel, Megan L. Fletcher, Urszula Łapińska, Krina Chawla, Evan Baker, Erin L. Attrill, Paul O’Neill et al. "Phage-induced efflux down-regulation boosts antibiotic efficacy". PLOS Pathogens 20, n. 6 (28 giugno 2024): e1012361. http://dx.doi.org/10.1371/journal.ppat.1012361.
Testo completoAbstract (sommario):
The interactions between a virus and its host vary in space and time and are affected by the presence of molecules that alter the physiology of either the host or the virus. Determining the molecular mechanisms at the basis of these interactions is paramount for predicting the fate of bacterial and phage populations and for designing rational phage-antibiotic therapies. We study the interactions between stationary phase Burkholderia thailandensis and the phage ΦBp-AMP1. Although heterogeneous genetic resistance to phage rapidly emerges in B. thailandensis, the presence of phage enhances the efficacy of three major antibiotic classes, the quinolones, the beta-lactams and the tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. We discovered that enhanced antibiotic efficacy is facilitated by reduced antibiotic efflux in the presence of phage. This new phage-antibiotic therapy allows for eradication of stationary phase bacteria, whilst requiring reduced antibiotic concentrations, which is crucial for treating infections in sites where it is difficult to achieve high antibiotic concentrations.
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Zamora, Paula F., Thomas G. Reidy, Catherine R. Armbruster, Ming Sun, Daria Van Tyne, Paul E. Turner, Jonathan L. Koff e Jennifer M. Bomberger. "Lytic bacteriophages induce the secretion of antiviral and proinflammatory cytokines from human respiratory epithelial cells". PLOS Biology 22, n. 4 (23 aprile 2024): e3002566. http://dx.doi.org/10.1371/journal.pbio.3002566.
Testo completoAbstract (sommario):
Phage therapy is a therapeutic approach to treat multidrug-resistant (MDR) infections that employs lytic bacteriophages (phages) to eliminate bacteria. Despite the abundant evidence for its success as an antimicrobial in Eastern Europe, there is scarce data regarding its effects on the human host. Here, we aimed to understand how lytic phages interact with cells of the airway epithelium, the tissue site that is colonized by bacterial biofilms in numerous chronic respiratory disorders. Using a panel of Pseudomonas aeruginosa phages and human airway epithelial cells (AECs) derived from a person with cystic fibrosis (CF), we determined that interactions between phages and epithelial cells depend on specific phage properties as well as physiochemical features of the microenvironment. Although poor at internalizing phages, the airway epithelium responds to phage exposure by changing its transcriptional profile and secreting antiviral and proinflammatory cytokines that correlate with specific phage families. Overall, our findings indicate that mammalian responses to phages are heterogenous and could potentially alter the way that respiratory local defenses aid in bacterial clearance during phage therapy. Thus, besides phage receptor specificity in a particular bacterial isolate, the criteria to select lytic phages for therapy should be expanded to include mammalian cell responses.
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Wang, Yuer, Huahao Fan e Yigang Tong. "Unveil the Secret of the Bacteria and Phage Arms Race". International Journal of Molecular Sciences 24, n. 5 (22 febbraio 2023): 4363. http://dx.doi.org/10.3390/ijms24054363.
Testo completoAbstract (sommario):
Bacteria have developed different mechanisms to defend against phages, such as preventing phages from being adsorbed on the surface of host bacteria; through the superinfection exclusion (Sie) block of phage’s nucleic acid injection; by restricting modification (R-M) systems, CRISPR-Cas, aborting infection (Abi) and other defense systems to interfere with the replication of phage genes in the host; through the quorum sensing (QS) enhancement of phage’s resistant effect. At the same time, phages have also evolved a variety of counter-defense strategies, such as degrading extracellular polymeric substances (EPS) that mask receptors or recognize new receptors, thereby regaining the ability to adsorb host cells; modifying its own genes to prevent the R-M systems from recognizing phage genes or evolving proteins that can inhibit the R-M complex; through the gene mutation itself, building nucleus-like compartments or evolving anti-CRISPR (Acr) proteins to resist CRISPR-Cas systems; and by producing antirepressors or blocking the combination of autoinducers (AIs) and its receptors to suppress the QS. The arms race between bacteria and phages is conducive to the coevolution between bacteria and phages. This review details bacterial anti-phage strategies and anti-defense strategies of phages and will provide basic theoretical support for phage therapy while deeply understanding the interaction mechanism between bacteria and phages.
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Leclerc, Quentin J., Jodi A. Lindsay e Gwenan M. Knight. "Modelling the synergistic effect of bacteriophage and antibiotics on bacteria: Killers and drivers of resistance evolution". PLOS Computational Biology 18, n. 11 (30 novembre 2022): e1010746. http://dx.doi.org/10.1371/journal.pcbi.1010746.
Testo completoAbstract (sommario):
Bacteriophage (phage) are bacterial predators that can also spread antimicrobial resistance (AMR) genes between bacteria by generalised transduction. Phage are often present alongside antibiotics in the environment, yet evidence of their joint killing effect on bacteria is conflicted, and the dynamics of transduction in such systems are unknown. Here, we combine in vitro data and mathematical modelling to identify conditions where phage and antibiotics act in synergy to remove bacteria or drive AMR evolution. We adapt a published model of phage-bacteria dynamics, including transduction, to add the pharmacodynamics of erythromycin and tetracycline, parameterised from new in vitro data. We simulate a system where two strains of Staphylococcus aureus are present at stationary phase, each carrying either an erythromycin or tetracycline resistance gene, and where multidrug-resistant bacteria can be generated by transduction only. We determine rates of bacterial clearance and multidrug-resistant bacteria appearance, when either or both antibiotics and phage are present at varying timings and concentrations. Although phage and antibiotics act in synergy to kill bacteria, by reducing bacterial growth antibiotics reduce phage production. A low concentration of phage introduced shortly after antibiotics fails to replicate and exert a strong killing pressure on bacteria, instead generating multidrug-resistant bacteria by transduction which are then selected for by the antibiotics. Multidrug-resistant bacteria numbers were highest when antibiotics and phage were introduced simultaneously. The interaction between phage and antibiotics leads to a trade-off between a slower clearing rate of bacteria (if antibiotics are added before phage), and a higher risk of multidrug-resistance evolution (if phage are added before antibiotics), exacerbated by low concentrations of phage or antibiotics. Our results form hypotheses to guide future experimental and clinical work on the impact of phage on AMR evolution, notably for studies of phage therapy which should investigate varying timings and concentrations of phage and antibiotics.
46
Sørensen, Patricia E., Duncan Y. K. Ng, Luc Duchateau, Hanne Ingmer, An Garmyn e Patrick Butaye. "Classification of In Vitro Phage–Host Population Growth Dynamics". Microorganisms 9, n. 12 (30 novembre 2021): 2470. http://dx.doi.org/10.3390/microorganisms9122470.
Testo completoAbstract (sommario):
The therapeutic use of bacteriophages (phage therapy) represents a promising alternative to antibiotics to control bacterial pathogens. However, the understanding of the phage–bacterium interactions and population dynamics seems essential for successful phage therapy implementation. Here, we investigated the effect of three factors: phage species (18 lytic E. coli-infecting phages); bacterial strain (10 APEC strains); and multiplicity of infection (MOI) (MOI 10, 1, and 0.1) on the bacterial growth dynamics. All factors had a significant effect, but the phage appeared to be the most important. The results showed seven distinct growth patterns. The first pattern corresponded to the normal bacterial growth pattern in the absence of a phage. The second pattern was complete bacterial killing. The remaining patterns were in-between, characterised by delayed growth and/or variable killing of the bacterial cells. In conclusion, this study demonstrates that the phage–host dynamics is an important factor in the capacity of a phage to eliminate bacteria. The classified patterns show that this is an essential factor to consider when developing a phage therapy. This methodology can be used to rapidly screen for novel phage candidates for phage therapy. Accordingly, the most promising candidates were phages found in Group 2, characterised by growth dynamics with high bacterial killing.
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Lucia-Sanz, Adriana, Shengyun Peng, Joey Leung, Animesh Gupta, Justin R. Meyer e Joshua S. Weitz. "Inferring strain-level mutational drivers of phage-bacteria interaction phenotypes arising during coevolutionary dynamics". Virus Evolution, 29 novembre 2024. http://dx.doi.org/10.1093/ve/veae104.
Testo completoAbstract (sommario):
Abstract The enormous diversity of bacteriophages and their bacterial hosts presents a significant challenge to predict which phages infect a focal set of bacteria. Infection is largely determined by complementary—and largely uncharacterized—genetics of adsorption, injection, cell take-over and lysis. Here we present a machine learning approach to predict phage-bacteria interactions trained on genome sequences of and phenotypic interactions amongst 51 Escherichia coli strains and 45 phage λ strains that coevolved in laboratory conditions for 37 days. Leveraging multiple inference strategies and without a priori knowledge of driver mutations, this framework predicts both who infects whom and the quantitative levels of infections across a suite of 2,295 potential interactions. We found that the most effective approach inferred interaction phenotypes from independent contributions from phage and bacteria mutations, accurately predicting 86% of interactions while reducing the relative error in the estimated strength of the infection phenotype by 40%. Feature selection revealed key phage λ and E. coli mutations that have a significant influence on the outcome of phage-bacteria interactions, corroborating sites previously known to affect phage λ infections, as well as identifying mutations in genes of unknown function not previously shown to influence bacterial resistance. The method’s success in recapitulating strain-level infection outcomes arising during coevolutionary dynamics may also help inform generalized approaches for imputing genetic drivers of interaction phenotypes in complex communities of phage and bacteria.
48
Molina, Felipe, Manuel Menor-Flores, Lucía Fernández, Miguel A. Vega-Rodríguez e Pilar García. "Systematic analysis of putative phage-phage interactions on minimum-sized phage cocktails". Scientific Reports 12, n. 1 (14 febbraio 2022). http://dx.doi.org/10.1038/s41598-022-06422-1.
Testo completoAbstract (sommario):
AbstractThe application of bacteriophages as antibacterial agents has many benefits in the “post-antibiotic age”. To increase the number of successfully targeted bacterial strains, phage cocktails, instead of a single phage, are commonly formulated. Nevertheless, there is currently no consensus pipeline for phage cocktail development. Thus, although large cocktails increase the spectrum of activity, they could produce side effects such as the mobilization of virulence or antibiotic resistance genes. On the other hand, coinfection (simultaneous infection of one host cell by several phages) might reduce the potential for bacteria to evolve phage resistance, but some antagonistic interactions amongst phages might be detrimental for the outcome of phage cocktail application. With this in mind, we introduce here a new method, which considers the host range and each individual phage-host interaction, to design the phage mixtures that best suppress the target bacteria while minimizing the number of phages to restrict manufacturing costs. Additionally, putative phage-phage interactions in cocktails and phage-bacteria networks are compared as the understanding of the complex interactions amongst bacteriophages could be critical in the development of realistic phage therapy models in the future.
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Kauffman, Kathryn M., William K. Chang, Julia M. Brown, Fatima A. Hussain, Joy Yang, Martin F. Polz e Libusha Kelly. "Resolving the structure of phage–bacteria interactions in the context of natural diversity". Nature Communications 13, n. 1 (18 gennaio 2022). http://dx.doi.org/10.1038/s41467-021-27583-z.
Testo completoAbstract (sommario):
AbstractMicrobial communities are shaped by viral predators. Yet, resolving which viruses (phages) and bacteria are interacting is a major challenge in the context of natural levels of microbial diversity. Thus, fundamental features of how phage-bacteria interactions are structured and evolve in the wild remain poorly resolved. Here we use large-scale isolation of environmental marine Vibrio bacteria and their phages to obtain estimates of strain-level phage predator loads, and use all-by-all host range assays to discover how phage and host genomic diversity shape interactions. We show that lytic interactions in environmental interaction networks (as observed in agar overlay) are sparse—with phage predator loads being low for most bacterial strains, and phages being host-strain-specific. Paradoxically, we also find that although overlap in killing is generally rare between tailed phages, recombination is common. Together, these results suggest that recombination during cryptic co-infections is an important mode of phage evolution in microbial communities. In the development of phages for bioengineering and therapeutics it is important to consider that nucleic acids of introduced phages may spread into local phage populations through recombination, and that the likelihood of transfer is not predictable based on lytic host range.
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Almeida, Gabriel M. F., Elina Laanto, Roghaieh Ashrafi e Lotta-Riina Sundberg. "Bacteriophage Adherence to Mucus Mediates Preventive Protection against Pathogenic Bacteria". mBio 10, n. 6 (19 novembre 2019). http://dx.doi.org/10.1128/mbio.01984-19.
Testo completoAbstract (sommario):
ABSTRACT Metazoans were proposed to host bacteriophages on their mucosal surfaces in a symbiotic relationship, where phages provide an external immunity against bacterial infections and the metazoans provide phages a medium for interacting with bacteria. However, scarce empirical evidence and model systems have left the phage-mucus interaction poorly understood. Here, we show that phages bind both to porcine mucus and to rainbow trout (Oncorhynchus mykiss) primary mucus, persist up to 7 days in the mucosa, and provide protection against Flavobacterium columnare. Also, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. This trade-off in bacterial virulence reveals ecological benefit of maintaining phages in the metazoan mucosal surfaces. Tests using other phage-bacterium pairs suggest that phage binding to mucus may be widespread in the biosphere, indicating its importance for disease, ecology, and evolution. This phenomenon may have significant potential to be exploited in preventive phage therapy. IMPORTANCE The mucosal surfaces of animals are habitat for microbes, including viruses. Bacteriophages—viruses that infect bacteria—were shown to be able to bind to mucus. This may result in a symbiotic relationship in which phages find bacterial hosts to infect, protecting the mucus-producing animal from bacterial infections in the process. Here, we studied phage binding on mucus and the effect of mucin on phage-bacterium interactions. The significance of our research is in showing that phage adhesion to mucus results in preventive protection against bacterial infections, which will serve as basis for the development of prophylactic phage therapy approaches. Besides, we also reveal that exposure to mucus upregulates bacterial virulence and that this is exploited by phages for infection, adding one additional layer to the metazoan-bacterium-phage biological interactions and ecology. This phenomenon might be widespread in the biosphere and thus crucial for understanding mucosal diseases, their outcome and treatment.