Journal articles: 'Staphylococcal membrane damaging toxins'

1

Popoff, Michel R. "Bacterial Toxins, Current Perspectives." Toxins 12, no. 9 (September 4, 2020): 570. http://dx.doi.org/10.3390/toxins12090570.

Full text

Abstract:

Toxins are the major pathogenicity factors produced by numerous bacteria involved in severe diseases in humans and animals. Certain pathogenic bacteria synthesize only one toxin which is responsible for all the symptoms and outcome of the disease. For example, botulinum toxins (BoNTs) and tetanus toxin (TeNT) are the unique causal factors of botulism and tetanus, respectively. Other bacteria attack the host organism by a set of multiple toxins which synergistically act to promote the disease. This is the case of Clostridium and Staphylococcus strains which secrete wide ranges of toxins such as pore-forming toxins, membrane phospholipid damaging toxins, and other cytotoxins and toxins interacting with the immune system involved in gangrene lesion generation.

APA, Harvard, Vancouver, ISO, and other styles

2

Watanabe, Masashi, Toshio Tomita, and Tatsuji Yasuda. "Membrane-damaging action of staphylococcal alpha-toxin on phospholipid-cholesterol liposomes." Biochimica et Biophysica Acta (BBA) - Biomembranes 898, no. 3 (April 1987): 257–65. http://dx.doi.org/10.1016/0005-2736(87)90065-4.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Nocadello, S., G. Minasov, L. Shuvalova, I. Dubrovska, E. Sabini, F. Bagnoli, G. Grandi, and W. F. Anderson. "Crystal structures of the components of theStaphylococcus aureusleukotoxin ED." Acta Crystallographica Section D Structural Biology 72, no. 1 (January 1, 2016): 113–20. http://dx.doi.org/10.1107/s2059798315023207.

Full text

Abstract:

Staphylococcal leukotoxins are a family of β-barrel, bicomponent, pore-forming toxins with membrane-damaging functions. These bacterial exotoxins share sequence and structural homology and target several host-cell types. Leukotoxin ED (LukED) is one of these bicomponent pore-forming toxins thatStaphylococcus aureusproduces in order to suppress the ability of the host to contain the infection. The recent delineation of the important role that LukED plays inS. aureuspathogenesis and the identification of its protein receptors, combined with its presence inS. aureusmethicillin-resistant epidemic strains, establish this leukocidin as a possible target for the development of novel therapeutics. Here, the crystal structures of the water-soluble LukE and LukD components of LukED have been determined. The two structures illustrate the tertiary-structural variability with respect to the other leukotoxins while retaining the conservation of the residues involved in the interaction of the protomers in the bipartite leukotoxin in the pore complex.

APA, Harvard, Vancouver, ISO, and other styles

4

BUTT, H. L., R. H. DUNSTAN, N. R. McGREGOR, T. K. ROBERTS, M. ZERBES, and I. J. KLINEBERG. "An association of membrane-damaging toxins from coagulase-negative staphylococci and chronic orofacial muscle pain." Journal of Medical Microbiology 47, no. 7 (July 1, 1998): 577–84. http://dx.doi.org/10.1099/00222615-47-7-577.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Escajadillo, Tamara, and Victor Nizet. "Pharmacological Targeting of Pore-Forming Toxins as Adjunctive Therapy for Invasive Bacterial Infection." Toxins 10, no. 12 (December 17, 2018): 542. http://dx.doi.org/10.3390/toxins10120542.

Full text

Abstract:

For many of the most important human bacterial infections, invasive disease severity is fueled by the cell damaging and pro-inflammatory effects of secreted pore-forming toxins (PFTs). Isogenic PFT-knockout mutants, e.g., Staphylococcus aureus lacking α-toxin or Streptococcus pneumoniae deficient in pneumolysin, show attenuation in animal infection models. This knowledge has inspired multi-model investigations of strategies to neutralize PFTs or counteract their toxicity as a novel pharmacological approach to ameliorate disease pathogenesis in clinical disease. Promising examples of small molecule, antibody or nanotherapeutic drug candidates that directly bind and neutralize PFTs, block their oligomerization or membrane receptor interactions, plug establishment membrane pores, or boost host cell resiliency to withstand PFT action have emerged. The present review highlights these new concepts, with a special focus on β-PFTs produced by leading invasive human Gram-positive bacterial pathogens. Such anti-virulence therapies could be applied as an adjunctive therapy to antibiotic-sensitive and -resistant strains alike, and further could be free of deleterious effects that deplete the normal microflora.

APA, Harvard, Vancouver, ISO, and other styles

6

Iliya, Sani, Jonathan Mwangi, Ronald Maathai, Mary Muriuki, and Christopher Wainaina. "Molecular Detection of Panton Valentine Leukocidin Toxin in Clinical Isolates of Staphylococcus aureus from Kiambu County, Kenya." International Journal of Microbiology 2020 (August 27, 2020): 1–8. http://dx.doi.org/10.1155/2020/3106747.

Full text

Abstract:

Panton–Valentine leukocidin gene is produced by Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus isolates as a pore-forming toxin is largely responsible for skin and soft tissue illnesses. MRSA produces PVL toxins through lukS and lukF proteins causing tissue necrosis by damaging membrane of the defense cells. Presence of PVL toxin was tested from the 54 S. aureus clinical isolates obtained from Thika and Kiambu Level 5 Hospitals, in Kiambu County, Kenya, by Geno Type® MRSA assay (Hain Life Science, Nehren, Germany). DNA was isolated from freshly harvested bacterial cultures by spin column using Geno Type DNA isolation kit. The detection of PVL toxins was performed by amplification of genomic DNA and by reverse hybridization that identifies PVL genes using Geno Type MRSA kit. Out of 138 samples that were collected from patients in Kiambu County, 54 S. aureus isolates were obtained, of which 14 (25.9%; 95% CI = 11.9–38.9) samples had PVL toxins. The isolates that were obtained from the female patients had a higher PVL toxin prevalence of 35.7%, while the isolates collected from the male patients had a lower prevalence of 15.4% (P=0.09). The pediatrics department had the highest PVL gene prevalence compared to outpatient department and surgical units (P=0.08). However, the age groups of patients and the hospital attended by patients showed no significant difference in terms of PVL gene prevalence (P=0.26). Therefore, the patients' gender and hospital units were not significantly associated with PVL gene prevalence (P=0.08). This study shows that PVL positive isolates occur in the sampled hospitals in the county and female as well as children must be taken into consideration among patients with wound infections when isolating S. aureus.

APA, Harvard, Vancouver, ISO, and other styles

7

Gabriunaite, Inga, Gintaras Valincius, Albinas Žilinskas, and Aušra Valiūnienė. "Tethered Bilayer Membrane Formation on Silanized Fluorine Doped Tin Oxide Surface." Journal of The Electrochemical Society 169, no. 3 (March 1, 2022): 037515. http://dx.doi.org/10.1149/1945-7111/ac5c96.

Full text

Abstract:

Silane compound was synthesized via click chemistry and a mixture of synthesis products without purification was used to form the self-assembled monolayers on metal oxide conducting films of fluorine doped tin oxide (FTO). Silanized FTO surfaces triggered rupture of multilamellar vesicles and formed electrically insulating tethered bilayer membranes (tBLMs). In contrast to well-known hybrid bilayer membranes on silane monolayers such as ones formed from octadecyltrichlorosilane, tBLMs on FTO contained water-ion reservoir between solid surface and phospholipid bilayer sheet. They demonstrated biological relevance and ability to reconstitute the pore-forming protein channels such as α-hemolysin from Staphylococcus aureus and melittin. The addition of cholesterol to tBLMs decreased the membrane-damaging effect of melittin, while the opposite was observed in the case of α-hemolysin. The tBLMs can be regenerated multiple times without losing their functionality. The described methodology (both synthesis and formation of anchor monolayer) can be extended to any oxide film surface by properly adjusting chemical composition of molecular anchor and silanization conditions. This makes the proposed biomimetic membrane system attractive for various applications including biomedical sensors for the detection of pore-forming toxins.

APA, Harvard, Vancouver, ISO, and other styles

8

Metcalf, Lee N., Neil R. McGregor, and Timothy K. Roberts. "Membrane Damaging Toxins from Coagulase-Negative Staphylococcus Are Associated with Self-Reported Temporomandibular Disorder (TMD) in Patients with Chronic Fatigue Syndrome." Journal of Chronic Fatigue Syndrome 12, no. 3 (January 2004): 25–43. http://dx.doi.org/10.1300/j092v12n03_03.

Full text

APA, Harvard, Vancouver, ISO, and other styles

9

Zainulabdeen, Shaimaa M. S., and Adian A. Dakl. ""Review Article Pathogenicity and virulence factors in Staphylococcus aureus." Muthanna Journal of Pure Science 8, no. 1 (January 13, 2021): 109–19. http://dx.doi.org/10.52113/2/08.01.2021/109-119.

Full text

Abstract:

"Staphylococcus aureus is a pathogen that resides in the skin and nasal membranes and can cause a broad spectrum of hospital-acquired infections. These diseases are becoming more common, and treating them has become much more complicated. The pathogen’s capacity to secret a variety of host-damaging virulence factors contributes to its pathogenicity. S. aureus destroys and supersedes immune cells throughout infection via toxins and virulence proteins, yielding non-neutralizing infective antibodies which already impede adaptive immunity. S. aureus has different biofilm-forming mechanisms on devices, necrotic bone tissue, bone marrow, and finally within the osteocyte lacuno-canicular networks of living bone (OLCN).This review focuses on gaining a better understanding of S. aureus toxin-based pathogenesis and its effects on infectious diseases.

APA, Harvard, Vancouver, ISO, and other styles

10

Olofsson, Anders, Hans Hebert, Urban Kavéus, and Monica Thelestam. "Staphylococcus aureus α-Toxin Crystals on Lipid Layers: Effects of Trypsin Treatment." Proceedings, annual meeting, Electron Microscopy Society of America 48, no. 1 (August 12, 1990): 106–7. http://dx.doi.org/10.1017/s0424820100179282.

Full text

Abstract:

α-toxin is a lethal, dermonecrotic, cytotoxic, and hemolytic protein which is secreted by most strains of Staphylococcus aureus . The biological effects are brought about by pertubation of membrane structures making them permeable to ions and small molecules. The structural basis for the mode of action is not known in detail. One hypothesis is that an oligomeric form of the toxin, observed both biochemically and by electron microscopy, circumscribe a hydrophilic pore through which transport can occur. Recent functional studies have demonstrated that oligomerization is a necessary but not a sufficient criterion for permeabilization. For example, trypsin treated α-toxin was, despite its lack of membrane damaging activity, able to form 200 kDa aggregates on mouse adrenocortical (Yl) tumor cells. In this work we have compared the structure of trypsin treated α-toxin with that of the intact toxin.α-toxin was purified from S. aureus strain wood 46 by isoelectric focussing and gel filtration. Tryptic toxin fragments (18 and 17 kD as determined by SDS-PAGE) were generated by digestion of native α-toxin (1 mg in 1.5 ml Tris buffered saline) with 30μg trypsin for 4 h at 37°C, pH 8.0. The reaction was terminated by the addition of 30μg lima beam trypsin inhibitor. Toxin specimens were applied to lipid layers pre-formed on carbon support films. Electron microscopy was performed after negative staining either with 1% Na-PTA (pH 7.0) or with a mixture of Na-PTA and glucose. Subsequent image processing of large coherent crystalline arrays produced correlation averaged projection maps. A three-dimensional model was obtained by collecting and combining data from tilted views.

APA, Harvard, Vancouver, ISO, and other styles

11

Callegan, Michelle C., Daniel C. Cochran, Scott T. Kane, Michael S. Gilmore, Myriam Gominet, and Didier Lereclus. "Contribution of Membrane-Damaging Toxins to Bacillus Endophthalmitis Pathogenesis." Infection and Immunity 70, no. 10 (October 2002): 5381–89. http://dx.doi.org/10.1128/iai.70.10.5381-5389.2002.

Full text

Abstract:

ABSTRACT Membrane-damaging toxins are thought to be responsible for the explosive clinical course of Bacillus endophthalmitis. This study analyzed the contribution of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific phospholipase C (PC-PLC) to the pathogenesis of experimental Bacillus endophthalmitis. Isogenic mutants were constructed by insertion of lacZ into Bacillus thuringiensis genes encoding PI-PLC (plcA) and PC-PLC (plcB). Rabbit eyes were injected intravitreally with 2 log10 CFU of strain BT407 (wild type), the PI-PLC mutant (BTplcA::lacZ), or the PC-PLC mutant (BTplcB::lacZ). The rates of decrease in retinal responses of eyes infected with the isogenic mutants were similar to that of wild type, with all infections resulting in elimination of retinal function by 18 h. Strain BT407 caused a significant increase in the latency of retinal responses at 6 h, but strains BTplcA::lacZ and BTplcB::lacZ did not. All strains elicited significant inflammatory cell influx into the anterior chamber by 12 h. Histologically, eyes infected with each strain were indistinguishable throughout the infection course. In this model, neither PI-PLC nor PC-PLC had an effect on the course or severity of experimental Bacillus endophthalmitis. Alterations in retinal responses early in infection may mark the beginnings of specific photoreceptor or glial cell dysfunction.

APA, Harvard, Vancouver, ISO, and other styles

12

Bernheimer, Alan W. "Some aspects of the history of membrane-damaging toxins." Medical Microbiology and Immunology 185, no. 2 (September 3, 1996): 59–63. http://dx.doi.org/10.1007/s004300050015.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Liu, Jie, Lina Kozhaya, Victor J. Torres, Derya Unutmaz, and Min Lu. "Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence." Journal of Biological Chemistry 295, no. 18 (March 16, 2020): 5944–59. http://dx.doi.org/10.1074/jbc.ra120.012697.

Full text

Abstract:

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

APA, Harvard, Vancouver, ISO, and other styles

14

Alouf, J. E., and C. Geoffroy. "Cholesterol binding family of the membrane-damaging, thiol-dependent bacterial protein toxins." Toxicon 33, no. 9 (September 1995): 1114. http://dx.doi.org/10.1016/0041-0101(95)93816-d.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Mondal, Anish Kumar, Pratima Verma, Kusum Lata, Mahendra Singh, Shamaita Chatterjee, and Kausik Chattopadhyay. "Sequence Diversity in the Pore-Forming Motifs of the Membrane-Damaging Protein Toxins." Journal of Membrane Biology 253, no. 5 (September 21, 2020): 469–78. http://dx.doi.org/10.1007/s00232-020-00141-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Ghelardi, Emilia, Francesco Celandroni, Sara Salvetti, Ersilia Fiscarelli, and Sonia Senesi. "Bacillus thuringiensis pulmonary infection: critical role for bacterial membrane-damaging toxins and host neutrophils." Microbes and Infection 9, no. 5 (April 2007): 591–98. http://dx.doi.org/10.1016/j.micinf.2007.02.001.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Oparin, Peter B., Kirill D. Nadezhdin, Antonina A. Berkut, Alexander S. Arseniev, Eugene V. Grishin, and Alexander A. Vassilevski. "Structure of purotoxin-2 from wolf spider: modular design and membrane-assisted mode of action in arachnid toxins." Biochemical Journal 473, no. 19 (September 27, 2016): 3113–26. http://dx.doi.org/10.1042/bcj20160573.

Full text

Abstract:

Traditionally, arachnid venoms are known to contain two particularly important groups of peptide toxins. One is disulfide-rich neurotoxins with a predominance of β-structure that specifically target protein receptors in neurons or muscle cells. The other is linear cationic cytotoxins that form amphiphilic α-helices and exhibit rather non-specific membrane-damaging activity. In the present paper, we describe the first 3D structure of a modular arachnid toxin, purotoxin-2 (PT2) from the wolf spider Alopecosa marikovskyi (Lycosidae), studied by NMR spectroscopy. PT2 is composed of an N-terminal inhibitor cystine knot (ICK, or knottin) β-structural domain and a C-terminal linear cationic domain. In aqueous solution, the C-terminal fragment is hyper-flexible, whereas the knottin domain is very rigid. In membrane-mimicking environment, the C-terminal domain assumes a stable amphipathic α-helix. This helix effectively tethers the toxin to membranes and serves as a membrane-access and membrane-anchoring device. Sequence analysis reveals that the knottin + α-helix architecture is quite widespread among arachnid toxins, and PT2 is therefore the founding member of a large family of polypeptides with similar structure motifs. Toxins from this family target different membrane receptors such as P2X in the case of PT2 and calcium channels, but their mechanism of action through membrane access may be strikingly similar.

APA, Harvard, Vancouver, ISO, and other styles

18

Verma, Pratima, Shraddha Gandhi, Kusum Lata, and Kausik Chattopadhyay. "Pore-forming toxins in infection and immunity." Biochemical Society Transactions 49, no. 1 (January 25, 2021): 455–65. http://dx.doi.org/10.1042/bst20200836.

Full text

Abstract:

The integrity of the plasma membranes is extremely crucial for the survival and proper functioning of the cells. Organisms from all kingdoms of life employ specialized pore-forming proteins and toxins (PFPs and PFTs) that perforate cell membranes, and cause detrimental effects. PFPs/PFTs exert their damaging actions by forming oligomeric pores in the membrane lipid bilayer. PFPs/PFTs play important roles in diverse biological processes. Many pathogenic bacteria secrete PFTs for executing their virulence mechanisms. The immune system of the higher vertebrates employs PFPs to kill pathogen-infected cells and transformed cancer cells. The most obvious consequence of membrane pore-formation by the PFPs/PFTs is the killing of the target cells due to the disruption of the permeability barrier function of the plasma membranes. PFPs/PFTs can also activate diverse cellular processes that include activation of the stress-response pathways, induction of programmed cell death, and inflammation. Upon attack by the PFTs, host cells may also activate pathways to repair the injured membranes, restore cellular homeostasis, and trigger inflammatory immune responses. In this article, we present an overview of the diverse cellular responses that are triggered by the PFPs/PFTs, and their implications in the process of pathogen infection and immunity.

APA, Harvard, Vancouver, ISO, and other styles

19

See, Raymond H., Gerald Krystal, and Anthony W. Chow. "Receptors for toxic shock syndrome toxin-1 and staphylococcal enterotoxin A on human blood monocytes." Canadian Journal of Microbiology 38, no. 9 (September 1, 1992): 937–44. http://dx.doi.org/10.1139/m92-151.

Full text

Abstract:

Staphylococcal toxic shock syndrome toxin-1 (TSST-1) as well as staphylococcal enterotoxin A (SEA) and B (SEB) have recently been shown to bind directly to the class II major histocompatibility antigen, HLA-DR. Whereas others have characterized TSST-1 and SEA binding to HLA-DR on transfected L cells or B lymphoma cell lines, we sought evidence for direct binding of TSST-1 and SEA to HLA-DR on purified human monocytes. A single class of high-affinity receptors was found for both TSST-1 (dissociation constant (Kd) 40 nM, 3.4 × 104 receptors per cell) and SEA (Kd 12 nM, 3.2 × 104 receptors per cell) on normal human monocytes. Affinity cross-linking of 125I-labeled toxins to monocytes revealed the presence of two membrane protein subunits with molecular masses consistent with the α and β chains of human HLA-DR (35 and 28 kDa, respectively). The anti-HLA-DR monoclonal antibody L243, but not L203 or 2.06, inhibited radiolabeled toxin binding to human monocytes and neutralized the mitogenic response of human T lymphocytes to both toxins. However, L243 was consistently more effective in blocking radiolabeled TSST-1 than SEA binding to human monocytes from the same donors, suggesting that TSST-1 and SEA may be binding to overlapping epitopes rather than to the same epitope on HLA-DR. Because TSST-1 and SEB bind to distinct epitopes on HLA-DR and because SEA cross competes with both TSST-1 and SEB on the HLA-DR receptor, we postulate that SEA occupies a binding site within HLA-DR that overlaps both TSST-1 and SEB. Future studies focused on receptor-mediated binding of these toxins to human monocytes and T lymphocytes from normal donors and toxic shock syndrome patients may reveal the underlying anomalies that predispose particular individuals to toxic shock syndrome. Key words: monocytes, staphylococcal toxic shock syndrome toxin-1, receptors, HLA-DR, staphylococcal enterotoxin A.

APA, Harvard, Vancouver, ISO, and other styles

20

Yarovinsky, Timur O., Martha M. Monick, Matthias Husmann, and Gary W. Hunninghake. "Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin." Infection and Immunity 76, no. 2 (December 10, 2007): 571–77. http://dx.doi.org/10.1128/iai.01088-07.

Full text

Abstract:

ABSTRACT Many bacterial pathogens, including Staphylococcus aureus, use a variety of pore-forming toxins as important virulence factors. Staphylococcal alpha-toxin, a prototype β-barrel pore-forming toxin, triggers the release of proinflammatory mediators and induces primarily necrotic death in susceptible cells. However, whether host factors released in response to staphylococcal infections may increase cell resistance to alpha-toxin is not known. Here we show that prior exposure to interferons (IFNs) prevents alpha-toxin-induced membrane permeabilization, the depletion of ATP, and cell death. Moreover, pretreatment with IFN-α decreases alpha-toxin-induced secretion of interleukin 1β (IL-1β). IFN-α, IFN-β, and IFN-γ specifically protect cells from alpha-toxin, whereas tumor necrosis factor alpha (TNF-α), IL-6, and IL-4 have no effects. Furthermore, we show that IFN-α-induced protection from alpha-toxin is not dependent on caspase-1 or mitogen-activated protein kinases, but requires protein synthesis and fatty acid synthase activity. Our results demonstrate that IFNs may increase cell resistance to staphylococcal alpha-toxin via the regulation of lipid metabolism and suggest that interferons play a protective role during staphylococcal infections.

APA, Harvard, Vancouver, ISO, and other styles

21

TOMITA, Noriko, Yoshiyuki KAMIO, and Makoto OHTA. "Membrane-Damaging Activity Against Various Phospholipid Liposomes by ^|^gamma;-hemolysin, Staphylococcal Two-Component Pore-Forming Cytolysin." Journal of Biomechanical Science and Engineering 7, no. 3 (2012): 292–304. http://dx.doi.org/10.1299/jbse.7.292.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Chatterjee, Anushila, Julia L. E. Willett, Gary M. Dunny, and Breck A. Duerkop. "Phage infection and sub-lethal antibiotic exposure mediate Enterococcus faecalis type VII secretion system dependent inhibition of bystander bacteria." PLOS Genetics 17, no. 1 (January 7, 2021): e1009204. http://dx.doi.org/10.1371/journal.pgen.1009204.

Full text

Abstract:

Bacteriophages (phages) are being considered as alternative therapeutics for the treatment of multidrug resistant bacterial infections. Considering phages have narrow host-ranges, it is generally accepted that therapeutic phages will have a marginal impact on non-target bacteria. We have discovered that lytic phage infection induces transcription of type VIIb secretion system (T7SS) genes in the pathobiont Enterococcus faecalis. Membrane damage during phage infection induces T7SS gene expression resulting in cell contact dependent antagonism of different Gram positive bystander bacteria. Deletion of essB, a T7SS structural component, abrogates phage-mediated killing of bystanders. A predicted immunity gene confers protection against T7SS mediated inhibition, and disruption of its upstream LXG toxin gene rescues growth of E. faecalis and Staphylococcus aureus bystanders. Phage induction of T7SS gene expression and bystander inhibition requires IreK, a serine/threonine kinase, and OG1RF_11099, a predicted GntR-family transcription factor. Additionally, sub-lethal doses of membrane targeting and DNA damaging antibiotics activated T7SS expression independent of phage infection, triggering T7SS antibacterial activity against bystander bacteria. Our findings highlight how phage infection and antibiotic exposure of a target bacterium can affect non-target bystander bacteria and implies that therapies beyond antibiotics, such as phage therapy, could impose collateral damage to polymicrobial communities.

APA, Harvard, Vancouver, ISO, and other styles

23

Zitzer, Alexander, Emily J. Westover, Douglas F. Covey, and Michael Palmer. "Differential interaction of the two cholesterol-dependent, membrane-damaging toxins, streptolysin O andVibrio choleraecytolysin, with enantiomeric cholesterol." FEBS Letters 553, no. 3 (September 24, 2003): 229–31. http://dx.doi.org/10.1016/s0014-5793(03)01023-8.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Międzobrodzki, Jacek. "The Role of Staphylococcus aureus in Secondary Infections in Patients with Atopic Dermatitis (AD)." Polish Journal of Microbiology 65, no. 3 (August 26, 2016): 253–59. http://dx.doi.org/10.5604/17331331.1215600.

Full text

Abstract:

Staphylococcus aureus colonizes the mucous membrane of the nasal vestibule of a significant number of healthy people. These microorganisms are opportunistic pathogens, that in favorable conditions, may cause infections of various course, location or manifestation. Secondary infections emerge in cases when other risk factors contribute to such a change. One of the diseases during which S. aureus changes its saprophytic character to a pathogenic one is atopic dermatitis (AD), an allergic skin condition of a chronic and recurrent nature. Patients with AD are highly predisposed to secondary staphylococcal infections due to active S. aureus colonization of the stratum corneum, damage of the skin barrier or a defective immune response. Microorganisms present in skin lesions destroy the tissue by secreting enzymes and toxins, and additionally stimulate secondary allergic reactions. The toxins secreted by strains of S. aureus also act as superantigens and penetrate the skin barrier contributing to a chronic inflammation of the atopic skin lesions. The S. aureus species also releases proinflammatory proteins, including enzymes that cause tissue damage. When initiating treatment it is particularly important to properly assess that the onset of the secondary bacterial infection is caused by S. aureus and thus justifying the inclusion of antibiotic therapy. Depending on the severity and extent of the staphylococcal infection, topical antibiotics are used, usually mupirocin or fusidic acid, or general antibiotic treatment is introduced. Another therapeutic strategy without antibiotics has given a positive effect in patients.

APA, Harvard, Vancouver, ISO, and other styles

25

Laventie, Benoît-Joseph, Cristina Potrich, Cédric Atmanène, Maher Saleh, Olivier Joubert, Gabriella Viero, Christoph Bachmeyer, et al. "p-Sulfonato-calix[n]arenes inhibit staphylococcal bicomponent leukotoxins by supramolecular interactions." Biochemical Journal 450, no. 3 (February 28, 2013): 559–71. http://dx.doi.org/10.1042/bj20121628.

Full text

Abstract:

PVL (Panton–Valentine leukocidin) and other Staphylococcus aureus β-stranded pore-forming toxins are important virulence factors involved in various pathologies that are often necrotizing. The present study characterized leukotoxin inhibition by selected SCns (p-sulfonato-calix[n]arenes): SC4, SC6 and SC8. These chemicals have no toxic effects on human erythrocytes or neutrophils, and some are able to inhibit both the activity of and the cell lysis by leukotoxins in a dose-dependent manner. Depending on the type of leukotoxins and SCns, flow cytometry revealed IC50 values of 6–22 μM for Ca2+ activation and of 2–50 μM for cell lysis. SCns were observed to affect membrane binding of class S proteins responsible for cell specificity. Electrospray MS and surface plasmon resonance established supramolecular interactions (1:1 stoichiometry) between SCns and class S proteins in solution, but not class F proteins. The membrane-binding affinity of S proteins was Kd=0.07–6.2 nM. The binding ability was completely abolished by SCns at different concentrations according to the number of benzenes (30–300 μM; SC8>SC6≫SC4). The inhibitory properties of SCns were also observed in vivo in a rabbit model of PVL-induced endophthalmitis. These calixarenes may represent new therapeutic avenues aimed at minimizing inflammatory reactions and necrosis due to certain virulence factors.

APA, Harvard, Vancouver, ISO, and other styles

26

González-Cabrera, Joel, Gema P. Farinós, Silvia Caccia, Mercedes Díaz-Mendoza, Pedro Castañera, Maria Giovanna Leonardi, Barbara Giordana, and Juan Ferré. "Toxicity and Mode of Action of Bacillus thuringiensis Cry Proteins in the Mediterranean Corn Borer, Sesamia nonagrioides (Lefebvre)." Applied and Environmental Microbiology 72, no. 4 (April 2006): 2594–600. http://dx.doi.org/10.1128/aem.72.4.2594-2600.2006.

Full text

Abstract:

ABSTRACT Sesamia nonagrioides is one of the most damaging pests of corn in Spain and other Mediterranean countries. Bt corn expressing the Bacillus thuringiensis Cry1Ab toxin is being grown on about 58,000 ha in Spain. Here we studied the mode of action of this Cry protein on S. nonagrioides (binding to specific receptors, stability of binding, and pore formation) and the modes of action of other Cry proteins that were found to be active in this work (Cry1Ac, Cry1Ca, and Cry1Fa). Binding assays were performed with 125I- or biotin-labeled toxins and larval brush border membrane vesicles (BBMV). Competition experiments indicated that these toxins bind specifically and that Cry1Aa, Cry1Ab, and Cry1Ac share a binding site. Cry1Ca and Cry1Fa bind to different sites. In addition, Cry1Fa binds to Cry1A's binding site with very low affinity and vice versa. Binding of Cry1Ab and Cry1Ac was found to be stable over time, which indicates that the observed binding is irreversible. The pore-forming activity of Cry proteins on BBMV was determined using the voltage-sensitive fluorescent dye DiSC3(5). Membrane permeability increased in the presence of the active toxins Cry1Ab and Cry1Fa but not in the presence of the nonactive toxin Cry1Da. In terms of resistance management, based on our results and the fact that Cry1Ca is not toxic to Ostrinia nubilalis, we recommend pyramiding of Cry1Ab with Cry1Fa in the same Bt corn plant for better long-term control of corn borers.

APA, Harvard, Vancouver, ISO, and other styles

27

Rivas, Amable J., Gisela von Hoven, Claudia Neukirch, Martina Meyenburg, Qianqian Qin, Sabine Füser, Klaus Boller, Manuel L. Lemos, Carlos R. Osorio, and Matthias Husmann. "Phobalysin, a Small β-Pore-Forming Toxin of Photobacterium damselae subsp. damselae." Infection and Immunity 83, no. 11 (August 24, 2015): 4335–48. http://dx.doi.org/10.1128/iai.00277-15.

Full text

Abstract:

ABSTRACTPhotobacterium damselaesubsp.damselae, an important pathogen of marine animals, may also cause septicemia or hyperaggressive necrotizing fasciitis in humans. We previously showed that hemolysin genes are critical for virulence of this organism in mice and fish. In the present study, we characterized thehlyAgene product, a putative small β-pore-forming toxin, and termed it phobalysin P (PhlyP), for “photobacterial lysin encoded on a plasmid.” PhlyP formed stable oligomers and small membrane pores, causing efflux of K+, with no significant leakage of lactate dehydrogenase but entry of vital dyes. The latter feature distinguished PhlyP from the relatedVibrio choleraecytolysin. Attack by PhlyP provoked a loss of cellular ATP, attenuated translation, and caused profound morphological changes in epithelial cells. In coculture experiments with epithelial cells,Photobacterium damselaesubsp.damselaeled to rapid hemolysin-dependent membrane permeabilization. Unexpectedly, hemolysins also promoted the association ofP. damselaesubsp.damselaewith epithelial cells. The collective observations of this study suggest that membrane-damaging toxins commonly enhance bacterial adherence.

APA, Harvard, Vancouver, ISO, and other styles

28

Kehoe, M. A., L. Miller, J. A. Walker, and G. J. Boulnois. "Nucleotide sequence of the streptolysin O (SLO) gene: structural homologies between SLO and other membrane-damaging, thiol-activated toxins." Infection and Immunity 55, no. 12 (1987): 3228–32. http://dx.doi.org/10.1128/iai.55.12.3228-3232.1987.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Singh, Avinash, Asar Ahmed, Kashi N. Prasad, Sonali Khanduja, Satyendra K. Singh, Janmejai K. Srivastava, and Namdeo S. Gajbhiye. "Antibiofilm and Membrane-Damaging Potential of Cuprous Oxide Nanoparticles against Staphylococcus aureus with Reduced Susceptibility to Vancomycin." Antimicrobial Agents and Chemotherapy 59, no. 11 (August 24, 2015): 6882–90. http://dx.doi.org/10.1128/aac.01440-15.

Full text

Abstract:

ABSTRACTThe antimicrobial effects of copper ions and salts are well known, but the effects of cuprous oxide nanoparticles (Cu2O-NPs) on staphylococcal biofilms have not yet been clearly revealed. The present study evaluated Cu2O-NPs for their antibacterial and antibiofilm activities against heterogeneous vancomycin-intermediateStaphylococcus aureus(hVISA) and vancomycin-intermediateS. aureus(VISA). Nanoscaled Cu2O, generated by solution phase technology, contained Cu2O octahedral nanoparticles. Field emission electron microscopy demonstrated particles with sizes ranging from 100 to 150 nm. Cu2O-NPs inhibited the growth ofS. aureusand showed antibiofilm activity. The MICs and minimum biofilm inhibitory concentrations ranged from 625 μg/ml to 5,000 μg/ml and from 2,500 μg/ml to 10,000 μg/ml, respectively. Exposure ofS. aureusto Cu2O-NPs caused leakage of the cellular constituents and increased uptake of ethidium bromide and propidium iodide. Exposure also caused a significant reduction in the overall vancomycin-BODIPY (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding and a decrease in the viable cell count in the presence of 7.5% sodium chloride. Cu2O-NP toxicity assessment by hemolysis assay showed no cytotoxicity at 625 to 10,000 μg/ml concentrations. The results suggest that Cu2O-NPs exert their action by disruption of the bacterial cell membrane and can be used as effective antistaphylococcal and antibiofilm agents in diverse medical devices.

APA, Harvard, Vancouver, ISO, and other styles

30

Brennan, Donna, Ying Hu, Walid Medhat, Alicia Dowling, and Mỹ G. Mahoney. "Superficial Dsg2 Expression Limits Epidermal Blister Formation Mediated by Pemphigus Foliaceus Antibodies and Exfoliative Toxins." Dermatology Research and Practice 2010 (2010): 1–10. http://dx.doi.org/10.1155/2010/410278.

Full text

Abstract:

Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-α, Dsg1-β, and, to a lesser extent, Dsg1-γ, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.

APA, Harvard, Vancouver, ISO, and other styles

31

Kundu, Nidhi, Swapnil Tichkule, Shashi Bhushan Pandit, and Kausik Chattopadhyay. "Disulphide bond restrains the C-terminal region of thermostable direct hemolysin during folding to promote oligomerization." Biochemical Journal 474, no. 2 (January 6, 2017): 317–31. http://dx.doi.org/10.1042/bcj20160728.

Full text

Abstract:

Pore-forming toxins (PFTs) are typically produced as water-soluble monomers, which upon interacting with target cells assemble into transmembrane oligomeric pores. Vibrio parahaemolyticus thermostable direct hemolysin (TDH) is an atypical PFT that exists as a tetramer in solution, prior to membrane binding. The TDH structure highlights a core β-sandwich domain similar to those found in the eukaryotic actinoporin family of PFTs. However, the TDH structure harbors an extended C-terminal region (CTR) that is not documented in the actinoporins. This CTR remains tethered to the β-sandwich domain through an intra-molecular disulphide bond. Part of the CTR is positioned at the inter-protomer interface in the TDH tetramer. Here we show that the truncation, as well as mutation, of the CTR compromise tetrameric assembly, and the membrane-damaging activity of TDH. Our study also reveals that intra-protomer disulphide bond formation during the folding/assembly process of TDH restrains the CTR to mediate its participation in the formation of inter-protomer contact, thus facilitating TDH oligomerization. However, once tetramerization is achieved, disruption of the disulphide bond does not affect oligomeric assembly. Our study provides critical insights regarding the regulation of the oligomerization mechanism of TDH, which has not been previously documented in the PFT family.

APA, Harvard, Vancouver, ISO, and other styles

32

Browne, Kylie A., Elizabeth Blink, Vivien R. Sutton, Christopher J. Froelich, David A. Jans, and Joseph A. Trapani. "Cytosolic Delivery of Granzyme B by Bacterial Toxins: Evidence that Endosomal Disruption, in Addition to Transmembrane Pore Formation, Is an Important Function of Perforin." Molecular and Cellular Biology 19, no. 12 (December 1, 1999): 8604–15. http://dx.doi.org/10.1128/mcb.19.12.8604.

Full text

Abstract:

ABSTRACT Granule-mediated cell killing by cytotoxic lymphocytes requires the combined actions of a membranolytic protein, perforin, and granule-associated granzymes, but the mechanism by which they jointly kill cells is poorly understood. We have tested a series of membrane-disruptive agents including bacterial pore-forming toxins and hemolytic complement for their ability to replace perforin in facilitating granzyme B-mediated cell death. As with perforin, low concentrations of streptolysin O and pneumolysin (causing <10%51Cr release) permitted granzyme B-dependent apoptosis of Jurkat and Yac-1 cells, but staphylococcal alpha-toxin and complement were ineffective, regardless of concentration. The ensuing nuclear apoptotic damage was caspase dependent and included cleavage of poly(ADP-ribose) polymerase, suggesting a mode of action similar to that of perforin. The plasma membrane lesions formed at low dose by perforin, pneumolysin, and streptolysin did not permit diffusion of fluorescein-labeled proteins as small as 8 kDa into the cell, indicating that large membrane defects are not necessary for granzymes (32 to 65 kDa) to enter the cytosol and induce apoptosis. The endosomolytic toxin, listeriolysin O, also effected granzyme B-mediated cell death at concentrations which produced no appreciable cell membrane damage. Cells pretreated with inhibitors of endosomal trafficking such as brefeldin A took up granzyme B normally but demonstrated seriously impaired nuclear targeting of granzyme B when perforin was also added, indicating that an important role of perforin is to disrupt vesicular protein trafficking. Surprisingly, cells exposed to granzyme B with perforin concentrations that produced nearly maximal 51Cr release (1,600 U/ml) also underwent apoptosis despite excluding a 8-kDa fluorescein-labeled protein marker. Only at concentrations of >4,000 U/ml were perforin pores demonstrably large enough to account for transmembrane diffusion of granzyme B. We conclude that pore formation may allow granzyme B direct cytosolic access only when perforin is delivered at very high concentrations, while perforin’s ability to disrupt endosomal trafficking may be crucial when it is present at lower concentrations or in killing cells that efficiently repair perforin pores.

APA, Harvard, Vancouver, ISO, and other styles

33

Wu, Guan-Lin, Yi-Jun Shi, Chia-Hui Huang, Yuan-Chin Lee, Liang-Jun Wang, Jing-Ting Chiou, Chi-Yu Lu, and Long-Sen Chang. "Status of Asp29 and Asp40 in the Interaction of Naja atra Cardiotoxins with Lipid Bilayers." Toxins 12, no. 4 (April 18, 2020): 262. http://dx.doi.org/10.3390/toxins12040262.

Full text

Abstract:

It is widely accepted that snake venom cardiotoxins (CTXs) target the plasma membranes of cells. In the present study, we investigated the role of Asp residues in the interaction of Naja atra cardiotoxin 1 (CTX1) and cardiotoxin 3 (CTX3) with phospholipid bilayers using chemical modification. CTX1 contains three Asp residues at positions 29, 40, and 57; CTX3 contains two Asp residues at positions 40 and 57. Compared to Asp29 and Asp40, Asp57 was sparingly modified with semi-carbazide, as revealed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass and mass/mass analyses. Thus, semi-carbazide-modified CTX1 (SEM-CTX1) mainly contained modified Asp29 and Asp40, while SEM-CTX3 contained modified Asp40. Compared to that of native toxins, trifluoroethanol easily induced structural transition of SEM-CTX1 and SEM-CTX3, suggesting that the structural flexibility of CTXs was constrained by Asp40. Modification of Asp29 and Asp40 markedly promoted the ability of CTX1 to induce permeability of cell membranes and lipid vesicles; CTX3 and SEM-CTX3 showed similar membrane-damaging activity. Modification of Asp residues did not affect the membrane-binding capability of CTXs. Circular dichroism spectra of SEM-CTX3 and CTX3 were similar, while the gross conformation of SEM-CTX1 was distinct from that of CTX1. The interaction of CTX1 with membrane was distinctly changed by Asp modification. Collectively, our data suggest that Asp29 of CTX1 suppresses the optimization of membrane-bound conformation to a fully active state and that the function of Asp40 in the structural constraints of CTX1 and CTX3 is not important for the manifestation of membrane-perturbing activity.

APA, Harvard, Vancouver, ISO, and other styles

34

Sugawara-Tomita, Noriko, Toshio Tomita, and Yoshiyuki Kamio. "Stochastic Assembly of Two-Component Staphylococcal γ-Hemolysin into Heteroheptameric Transmembrane Pores with Alternate Subunit Arrangements in Ratios of 3:4 and 4:3." Journal of Bacteriology 184, no. 17 (September 1, 2002): 4747–56. http://dx.doi.org/10.1128/jb.184.17.4747-4756.2002.

Full text

Abstract:

ABSTRACT Self-assembling, pore-forming toxins from Staphylococcus aureus are illustrative molecules for the study of the assembly and membrane insertion of oligomeric transmembrane proteins. On the basis of previous studies, we have shown that the two-component γ-hemolysin assembles from LukF (or Hlg1, 34 kDa) and Hlg2 (32 kDa) to form ring-shaped transmembrane pores of ca. 200 kDa. Here we show that LukF and Hlg2 assemble in a stochastic manner to form alternate complexes with subunit stoichiometries of 3:4 and 4:3. High-resolution electron microscopic images of negatively stained pore complexes clearly revealed a heptameric structure. When adjacent monomers in the pore complexes were randomly cross-linked by using glutaraldehyde, LukF-LukF, LukF-Hlg2, and Hlg2-Hlg2 dimers were detected in an approximate ratio of 1:12:1, suggesting that LukF and Hlg2 were alternately arranged in the pore complex in molar ratios of 3:4 and 4:3. The alternate arrangements of LukF and Hlg2 in molar ratios of 3:4 and 4:3 were also visualized under electron microscope with the pore complexes consisting of glutathione S-transferase fusion protein of LukF or Hlg2 and wild-type protein of Hlg2 or LukF, respectively.

APA, Harvard, Vancouver, ISO, and other styles

35

Frolova, V. V., N. M. Chernov, D. Yu Ivkin, A. M. Rumyantsev, and S. V. Gurina. "Identifying possible target of action of 4,4a-dihydroxanthones in bacterial cells." Journal of microbiology, epidemiology and immunobiology 98, no. 5 (November 2, 2021): 558–66. http://dx.doi.org/10.36233/0372-9311-118.

Full text

Abstract:

Introduction. Partially hydrogenated derivatives of xanthone, dihydroxanthones, are being intensively studied. They are of interest due to their antimicrobial, antitumor, and antioxidant effects. Many researches are focused on the study of the cytotoxicity of dihydroxanthones and very little information is available on their antimicrobial activity. Therefore, the study of the antimicrobial activity and mechanism of action of new synthetic derivatives of 4,4a-dihydroxanthone is relevant. Preliminary studies have demonstrated that 4,4a-dihydroxanthones are active against gram-positive bacteria and have a pronounced anti-staphylococcal effect. Namely, 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone (BDC-DX) was shown to be the most active derivative.Aim of the study was to determine the possible target of action of the active derivative of BDC-DX in bacterial cells and its acute toxicity.Materials and methods. The method of measuring the intensity of absorption of the crystal violet dye by bacteria cells was used to prove the effect of BDC-DX on the permeability of the cytoplasmic membrane in bacterial cells. The plasma coagulase activity of Staphylococcus aureus was tested under the action of dihydroxanthone to determine the effect of dihydroxanthone on the process of protein synthesis. Plasmid DNA digestion method was used to study the effect of the compound on bacterial DNA. The acute toxicity of BDC-DX was determined by the express method of V.B. Prozorovsky.Results and discussion. BDC-DX increased the permeability of the cytoplasmic membrane of S. aureus. Dihydroxanthone did not directly affect the plasma coagulase activity of Staphylococcus and showed a weak damaging effect on bacterial DNA. The compound induced breaks in plasmid DNA at a very high concentration — 1 mM or 384 pg/ml and higher. BDC-DX is a low-toxic compound (the average lethal dose for oral administration of the compound is 1710 ± 170 mg/kg, the average lethal dose for intraperitoneal administration of the compound is 116.9 ± 13.3 mg/kg).Conclusion. For the first time, in-depth study of the possible mechanism of action of a new synthetic biologically active compound from the group of 4,4a- dihydroxanthones, BDC-DX, was conducted. A likely target of 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone in S. aureus cells is the cytoplasmic membrane. BDC-DX did not affect the process of protein synthesis, namely the activity of the plasma coagulase enzyme. The compound had no pronounced damaging effect on bacterial DNA. It was found that 4,4a-dihydroxanthone refers to low-toxic compounds.

APA, Harvard, Vancouver, ISO, and other styles

36

Grimminger, F., F. Rose, U. Sibelius, M. Meinhardt, B. Pötzsch, R. Spriestersbach, S. Bhakdi, N. Suttorp, and W. Seeger. "Human endothelial cell activation and mediator release in response to the bacterial exotoxins Escherichia coli hemolysin and staphylococcal alpha-toxin." Journal of Immunology 159, no. 4 (August 15, 1997): 1909–16. http://dx.doi.org/10.4049/jimmunol.159.4.1909.

Full text

Abstract:

Abstract Escherichia coli hemolysin (HlyA) and Staphylococcus aureus alpha-toxin are membrane-perturbating bacterial exotoxins that have been implicated as significant virulence factors in human diseases. We investigated the capacity of these toxins to cause cell activation and mediator release in human endothelial cells, compared with the efficacies of thrombin and the Ca2+ ionophore A23187. Concentration ranges tested were 1 to 1000 ng/ml (HlyA), 0.01 to 10 micro/ml (alpha-toxin), 0.01 to 10 U/ml (thrombin), and 0.01 to 10 microM (A23187). All stimuli caused dose-dependent generation of platelet-activating factor, nitric oxide, and prostaglandin I2. HlyA and thrombin effected time- and dose-dependent accumulation of large quantities of inositol phosphates, with maximum effects at 100 ng/ml and 1 U/ml, respectively. Corresponding time course and dose dependency were noted for HlyA-elicited diacylglycerol formation. In contrast, only the highest concentrations of alpha-toxin (10 microg/ml) and A23187 (10 microM) effected some moderate inositol phosphate accumulation, and this was suppressed in the presence of the platelet-activating factor antagonist WEB 2086. Metabolic and secretory responses elicited by alpha-toxin were dependent on the presence of extracellular Ca2+. We conclude that both HlyA and alpha-toxin are potent inductors of inflammatory and vasodilatory mediators in human endothelial cells. HlyA-elicited effects may proceed predominantly via activation of the phosphatidylinositol hydrolysis-related signal transduction pathway, whereas transmembrane Ca2+ flux appears to be the major event underlying the release of mediators in response to alpha-toxin. These toxin properties may contribute to vasoregulatory and inflammatory disturbances encountered in states of severe infection and sepsis.

APA, Harvard, Vancouver, ISO, and other styles

37

Werner, S., D. A. Colin, M. Coraiola, G. Menestrina, H. Monteil, and G. Prévost. "Retrieving Biological Activity from LukF-PV Mutants Combined with Different S Components Implies Compatibility between the Stem Domains of These Staphylococcal Bicomponent Leucotoxins." Infection and Immunity 70, no. 3 (March 2002): 1310–18. http://dx.doi.org/10.1128/iai.70.3.1310-1318.2002.

Full text

Abstract:

ABSTRACT Bicomponent leucotoxins, such as Panton-Valentine leucocidin, are composed of two classes of proteins, a class S protein such as LukS-PV, which bears the cell membrane binding function, and a class F protein such as LukF-PV, which interacts to form a bipartite hexameric pore. These leucotoxins induce cell activation, linked to a Ca2+ influx, and pore formation as two consecutive and independently inhibitable events. Knowledge of the LukF-PV monomer structure has indicated that the stem domain is folded into three antiparallel β-strands in the water-soluble form and has to refold into a transmembrane β-hairpin during pore formation. To investigate the requirements for the cooperative assembly of the stems of the S and F components to produce biological activity, we introduced multiple deletions or single point mutations into the stem domains of LukF-PV and HlgB. While the binding of the mutated proteins was weakly dependent on these changes, Ca2+ influx and pore formation were affected differently, confirming that they are independent events. Ca2+ entry into human polymorphonuclear cells requires oligomerization and may follow the formation of a prepore. The activity of some of the LukF-PV mutants, carrying the shorter deletions, was actually improved. This demonstrated that a crucial event in the action of these toxins is the transition of the prefolded stem into the extended β-hairpins and that this step may be facilitated by small deletions that remove some of the interactions stabilizing the folded structure.

APA, Harvard, Vancouver, ISO, and other styles

38

Andersson, M. A., R. Mikkola, J. Helin, M. C. Andersson, and M. Salkinoja-Salonen. "A Novel Sensitive Bioassay for Detection ofBacillus cereus Emetic Toxin and Related Depsipeptide Ionophores." Applied and Environmental Microbiology 64, no. 4 (April 1, 1998): 1338–43. http://dx.doi.org/10.1128/aem.64.4.1338-1343.1998.

Full text

Abstract:

ABSTRACT Of the toxins produced by Bacillus cereus, the emetic toxin is likely the most dangerous but, due to the lack of a suitable assay, the least well known. In this paper, a new, sensitive, inexpensive, and rapid bioassay for detection of the emetic toxin ofB. cereus is described. The assay is based on the loss of motility of boar spermatozoa upon 24 h of exposure to extracts of emetic B. cereus strains or contaminated food. The paralyzed spermatozoa exhibited swollen mitochondria, but no depletion of cellular ATP or damage to plasma membrane integrity was observed. Analysis of the purified toxin by electrospray tandem mass spectrometry showed that it was a dodecadepsipeptide with a mass fragmentation pattern similar to that described for cereulide. The 50% effective concentration of the purified toxin to boar spermatozoa was 0.5 ng of purified toxin ml of extended boar semen−1. This amount corresponds to 104 to 105 CFU of B. cereus cells. No toxicity was detected for 27 other B. cereus strains up to 108 CFU ml−1. The detection limit for food was 3 g of rice containing 106 to 107 CFU of emetic B. cereusper gram. Effects similar to those provoked by emetic B. cereus toxin were also induced in boar spermatozoa by valinomycin and gramicidin at 2 and 3 ng ml of extended boar semen−1, respectively. The symptoms provoked by the toxin in spermatozoa indicated that B. cereus emetic toxin was acting as a membrane channel-forming ionophore, damaging mitochondria and blocking the oxidative phosphorylation required for the motility of boar spermatozoa.

APA, Harvard, Vancouver, ISO, and other styles

39

Anderson, George P., Lisa C. Shriver-Lake, Jinny L. Liu, and Ellen R. Goldman. "Integrating Single Domain Antibodies into Field-Deployable Rapid Assays." Antibodies 11, no. 4 (October 17, 2022): 64. http://dx.doi.org/10.3390/antib11040064.

Full text

Abstract:

Single domain antibodies (sdAb) are the recombinant variable heavy domains derived from camelid heavy-chain antibodies. While they have binding affinities equivalent to conventional antibodies, sdAb are only one-tenth the size and possess numerous advantages such as excellent thermal stability with the ability to refold following denaturation, and inexpensive production in Escherichia coli or yeast. However, their small size does have drawbacks, one being that they can lose activity upon attachment or adsorption to surfaces, or may fail to adsorb efficiently, as they are highly soluble. This can make the transition from using conventional antibodies to sdAb nontrivial for assay development. Specifically, it is often necessary to re-optimize the protocols and tailor the recombinant sdAb through protein engineering to function efficiently in handheld assays, which currently are utilized for point of care testing and field applications. This work focuses on optimizing the integration of sdAb into rapid vertical flow assays. To achieve this goal, we engineered sdAb-based constructs and developed general protocols for the attachment of the sdAb to both gold nanoparticles and a support membrane. We achieved a limit of detection of 0.11 µg/mL for toxins staphylococcal enterotoxin B and ricin, both potential biothreat agents. Additionally, we demonstrated the ability to detect the nucleocapsid protein of SARS-CoV-2, a common target of antigen tests for COVID-19.

APA, Harvard, Vancouver, ISO, and other styles

40

Berube, Bryan J., Georgia R. Sampedro, Michael Otto, and Juliane Bubeck Wardenburg. "Thepsmα Locus Regulates Production of Staphylococcus aureus Alpha-Toxin during Infection." Infection and Immunity 82, no. 8 (May 27, 2014): 3350–58. http://dx.doi.org/10.1128/iai.00089-14.

Full text

Abstract:

ABSTRACTStaphylococcus aureusis a leading cause of human bacterial infection, causing a wide spectrum of disease ranging from skin and soft tissue infections to life-threatening pneumonia and sepsis.S. aureustoxins play an essential role in disease pathogenesis, contributing to both immunomodulation and host tissue injury. Prominent among these toxins are the membrane-active pore-forming cytolysin alpha-toxin (Hla) and the amphipathic α-helical phenol-soluble modulin (PSM) peptides. As deletion of either thehlaorpsmlocus leads to a phenotypically similar virulence defect in skin and soft tissue infection, we sought to determine the relative contribution of each locus to disease pathogenesis. Here we show that production of Hla can be modulated by PSM expression. AnS. aureusmutant lacking PSM expression exhibits a transcriptional delay inhlamRNA production and therefore fails to secrete normal levels of Hla at early phases of growth. This leads to attenuation of virulencein vitroand in murine skin and lung models of infection, correlating with reduced recovery of Hla from host tissues. Production of Hla and restoration of staphylococcal virulence can be achieved in thepsmmutant by plasmid-driven overexpression ofhla. Our study suggests the coordinated action of Hla and PSMs in host tissue during early pathogenesis, confirming a major role for Hla in epithelial injury duringS. aureusinfection. These findings highlight the possibility that therapeutics targeting PSM production may simultaneously prevent Hla-mediated tissue injury.

APA, Harvard, Vancouver, ISO, and other styles

41

Charla, Rajitha, Priyanka P. Patil, Arati A. Bhatkande, Nisha R. Khode, Venkanna Balaganur, Harsha V. Hegde, Darasaguppe R. Harish, and Subarna Roy. "In Vitro and In Vivo Inhibitory Activities of Selected Traditional Medicinal Plants against Toxin-Induced Cyto- and Entero- Toxicities in Cholera." Toxins 14, no. 10 (September 20, 2022): 649. http://dx.doi.org/10.3390/toxins14100649.

Full text

Abstract:

Careya arborea, Punica granatum, Psidium guajava, Holarrhena antidysenterica, Aegle marmelos, and Piper longum are commonly used traditional medicines against diarrhoeal diseases in India. This study investigated the inhibitory activity of these plants against cytotoxicity and enterotoxicity induced by toxins secreted by Vibrio cholerae. Cholera toxin (CT) and non-membrane damaging cytotoxin (NMDCY) in cell free culture filtrate (CFCF) of V. cholerae were quantified using GM1 ELISA and cell-based assays, respectively. Hydro-alcoholic extracts of these plants and lyophilized juice of P. granatum were tested against CT-induced elevation of cAMP levels in CHO cell line, binding of CT to ganglioside GM1 receptor and NMDCY-induced cytotoxicity. Significant reduction of cAMP levels in CFCF treated CHO cell line was observed for all extracts except P. longum. C. arborea, P. granatum, H. antidysenterica and A. marmelos showed >50% binding inhibition of CT to GM1 receptor. C. arborea, P. granatum, and P. guajava effectively decreased cytotoxicity and morphological alterations caused by NMDCY in CHO cell line. Further, the efficacy of these three plants against CFCF-induced enterotoxicity was seen in adult mice ligated-ileal loop model as evidenced by decrease in volume of fluid accumulation, cAMP levels in ligated-ileal tissues, and histopathological changes in intestinal mucosa. Therefore, these plants can be further validated for their clinical use against cholera.

APA, Harvard, Vancouver, ISO, and other styles

42

Gomes, Amanda, Leticia Monica Coimbra Gaziola, Luciana Knop, Rosa Andrea Nogueira Laiso, and Durvanei Augusto Maria. "Effect of Snake Venom Metalloprotease Desintegrin in Hepatocarcinoma Tumor Cells." JOURNAL OF BIOENGINEERING AND TECHNOLOGY APPLIED TO HEALTH 2, no. 4 (February 4, 2020): 112–22. http://dx.doi.org/10.34178/jbth.v2i4.89.

Full text

Abstract:

Hepatocellular carcinoma is the third leading cause of cancer-related death in the world. This cancer is associated with cirrhosis following the hepatitis B or C virus infection, alcohol addiction, metabolic liver disease and exposure to dietary toxins such as aflatoxins and aristolochic acid. Studies demonstrate the integration of the HBV genome into liver cell DNA, including cases of patients with HBV-negative serology. Despite advances in prevention techniques, screening, and technology in cancer diagnosis and treatments, the incidence and mortality remain worrisome. Therefore, this research is significant due to the contribution of the development of new biological agents that can be used as monotherapy or adjuvant chemotherapy. Jararhagin, a snake toxin isolated from Bothrops jararaca venom, has been the subject of many studies seeking alternatives for the treatment of cancer. This protein contains the cysteine-rich disintegrin-like metalloproteinase domains and desirable functions to combat tumor cells, such as promoting acute inflammation, damaging the vascular endothelium through the zinc-dependent catalytic domain (responsible for hemorrhagic function) and enzymatically degrading the constituents of the endothelial basement membrane. Due to the antitumor effects of jararhagin presented in previous research, this study aimed to describe the possible antitumor effects of this snake metalloprotease in the murine liver tumor, intending to propose a new therapeutic option in the human liver tumor.

APA, Harvard, Vancouver, ISO, and other styles

43

Sung, Chih-Chien, Yu-Chuan Hsu, Chun-Chi Chen, Yuh-Feng Lin, and Chia-Chao Wu. "Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease." Oxidative Medicine and Cellular Longevity 2013 (2013): 1–15. http://dx.doi.org/10.1155/2013/301982.

Full text

Abstract:

Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

APA, Harvard, Vancouver, ISO, and other styles

44

Liu, Fang, Jing Huang, and J. Evan Sadler. "Shiga Toxin 1(Stx1) Stimulates Endothelial Cell VWF Secretion through a Ca2+/PKC Signaling Pathway That Does Not Require the Active Toxin Stx1A Subunit." Blood 112, no. 11 (November 16, 2008): 3931. http://dx.doi.org/10.1182/blood.v112.11.3931.3931.

Full text

Abstract:

Abstract Shiga toxins (Stx) consist of 5 B (binding) subunits that interact with cell surface globotriaosylceramide (Gb3), and a single A subunit that is retrotranslocated into the cytoplasm where it enzymatically inactivates ribosomal RNA. E. coli O157:H7 can express several variants of Shiga toxin (Stx) that cause hemolytic uremic syndrome (HUS) by damaging renal microvascular endothelium. The Stx A subunit is required for cytopathic effects on endothelium. In addition, Stx causes fatal thrombotic microangiopathy in ADAMTS13-deficient mice, but not in wild-type mice, and this effect requires the presence of von Willebrand factor (VWF). When added to cultured human endothelial cells under conditions of laminar flow, Stx rapidly induces the acute secretion of long strings of VWF that attach to the cell surface and bind platelets with high affinity, which suggests that VWF-induced platelet aggregation might contribute to the pathogenesis of HUS. Whether VWF secretion depends on ribotoxic stress is unknown, and the mechanism of Stx-induced VWF secretion has not been characterized. To address these questions, we investigated VWF secretion by human umbilical vein endothelial cells (HUVECs) treated with Stx1 holotoxin (AB5) or binding subunits (B5). Recombinant Stx1 B5 was expressed in E. coli and purified to homogeneity. The pentameric composition and purity of B5 preparations were demonstrated by gel filtration chromatography and Western blotting. Endotoxin was removed from Stx AB5 and B5 preparations by affinity chromatography. HUVECs were perfused in a parallel plate flow chamber with fluorescently labeled anti-VWF and Stx preparations, and secreted VWF strings were visualized in real time by immunofluorescence microscopy. Unexpectedly, we found that Stx1 B5 and Stx1 AB5 were equally potent in stimulating the secretion of VWF strings. String formation was maximal after 5 min and was blocked by soluble analogs of Gb3 or anti-Stx1 B subunit antibodies. Pretreatment of HUVECs with a chelator of intracellular Ca2+ (0.1 mM BAPTA-AM, 30 min), a phospholipase C (PLC) inhibitor (5 μM U73122, 15 min), or a protein kinase C inhibitor (50 nM staurosporine, 30 min) decreased the secretion of VWF strings by 95%, 82%, or 90%, respectively. Treatment with a protein kinase A inhibitor (5 μM H89, 30 min) did not affect VWF string formation. To more directly assess Stx1-induced PLC activation, HUVECs were transfected with a plasmid expressing a PLC-delta PH domain-GFP construct, which binds membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2). When HUVECs were observed by confocal microscopy, both Stx1 AB5 and Stx1 B5 caused a rapid (<60 s) redistribution of fluorescent signal from plasma membrane to cytosol, indicating the acute activation of PLC and hydrolysis of PIP2. In addition, Stx1 AB5 or B5 induced a transient rise in intracellular Ca2+ level that peaked by 30 sec and declined to baseline over 5 min. Stx1-induced Ca2+ transients were comparable to those induced by 0.1 mM histamine or 1 U/ml thrombin. Stx-induced Ca2+ responses were inhibited by BAPTA-AM or U73122, but not by staurosporine or H89. Treatment with Stx1 AB5 or B5 had no effect on intracellular levels of cAMP. These results indicate that Stx1 B subunits stimulate VWF secretion through a previously unsuspected signaling pathway that involves binding to cell surface Gb3, PIP2 hydrolysis by PLC, increased intracellular Ca2+, and activation of PKC. Therefore, Stx1 secreted by enterohemorrhagic E. coli may contribute to the pathogenesis of HUS through at least two mechanisms that affect microvascular endothelium: cell death caused by A subunit-induced ribotoxic stress, and VWF secretion caused by an independent B subunit-induced cell signaling pathway.

APA, Harvard, Vancouver, ISO, and other styles

45

Педдер, В. В., А. А. Голубицких, Р. Н. Голых, Е. В. Хрусталева, С. И. Постольник, and Е. Г. Галянская. "OZONE / NO-ULTRASONIC METHOD IN COMBINATION WITH PHOTOCHROM RADIATION AND ANTIOXIDANTS In the treatment of patients with age-related macular degeneration of the retina." Южно-Сибирский научный вестник, no. 5(39) (October 31, 2021): 3–11. http://dx.doi.org/10.25699/sssb.2021.39.5.021.

Full text

Abstract:

На сегодняшний день одной из лидирующих причин инвалидности по зрению является возрастная макулярная дегенерация сетчатки (ВМД). Заболевание характеризуется преимущественным поражением хориокапиллярного слоя, мембраны Бруха и пигментного эпителия сетчатки, с последующим вовлечением фоторецепторов. За последнее десятилетие отмечается существенный рост частоты возникновения данной патологии как в пожилом, так и в молодом возрасте. Различают сухую и влажную форму ВМД. Повреждающие факторы различной этиологии запускают каскад патогенетический реакций, которые приводят к необратимой потере центрального зрения. В патогенезе заболевания существенная роль принадлежит окислительному стрессу, вследствие нарушения баланса между окислительными и антиоксидантными системами, вызывающего нарушение целостности комплекса фоторецепторов и пигментного эпителия сетчатки. Нарушение микроциркуляции в наружных слоях сетчатки приводит к накоплению эндотоксинов. Лимфатическая система, как одна из важнейших саногенно-потентных функций организма, участвует в купировании эндотоксикоза у больных ВМД за счёт лимфатической сорбции токсинов непосредственно в тканях с помощью лимфатических капилляров заинтересованного лимфорегиона. Отсутствие достаточно эффективных методов лечения макулодистрофии сетчатки глаза, позволяющих повысить зрительную функцию и предотвратить прогрессирование слепоты у пациентов, стимулирует поиск методов, использующих комплексное воздействие на патологически изменённые ткани глаза. В статье представлено обоснование комбинированного озон/NO-ультразвукового метода в сочетании с фотохромным и лазерным излучениями и антиоксидантами в лечении макулодистрофии сетчатки, позволяющими воздействовать на сетчатку глаз, как через слизистую полостей носа, так и поверхностно через кожные покровы лица и шеи в заинтересованных областях проекций лимфатических узлов и интерстиция по ходу отводящих от зрительного анализатора лимфатических сосудов. Предложенный метод лечения больных с ВМД позволяет осуществлять комбинированное лечебное воздействие комплексом физических и физико-химических факторов на дистрофически изменённую сетчатку глаз для купирования патологического процесса. Today, age-related macular degeneration of the retina (AMD) is one of the leading causes of vision disability. The disease is characterized by a predominant lesion of the choriocapillary layer, Bruch's membrane and retinal pigment epithelium, followed by the involvement of photoreceptors. Over the past decade, there has been a significant increase in the incidence of this pathology both in old and young age. Distinguish between dry and wet form of AMD. Damaging factors of various etiologies trigger a cascade of pathogenetic reactions that lead to irreversible loss of central vision. In the pathogenesis of the disease, an essential role belongs to oxidative stress, due to an imbalance between oxidative and antioxidant systems, which causes a violation of the integrity of the complex of photoreceptors and retinal pigment epithelium. Violation of microcirculation in the outer layers of the retina leads to the accumulation of endotoxins. The lymphatic system, as one of the most important sanogenic-potential functions of the body, is involved in the relief of endotoxicosis in patients with AMD due to the lymphatic sorption of toxins directly in the tissues with the help of the lymphatic capillaries of the interested lymph region. The lack of sufficiently effective methods for treating macular degeneration of the retina, allowing to increase visual function and prevent the progression of blindness in patients, stimulates the search for methods that use a complex effect on pathologically altered eye tissues. The article presents the rationale for the combined ozone / NO-ultrasound method in combination with photochromic and laser radiation and antioxidants in the treatment of macular degeneration of the retina, allowing to influence the retina, both through the nasal mucosa and superficially through the skin of the face and neck in zainte -resolved areas of the projections of the lymph nodes and interstitium along the lymphatic vessels diverting from the visual analyzer. The proposed method of treating patients with AMD allows for a combined therapeutic effect of a complex of physical and physicochemical factors on the dystrophically altered retina to arrest the pathological process.

APA, Harvard, Vancouver, ISO, and other styles

46

Radzieta, Michael, Matthew Malone, Mehtab Ahmad, Hugh G. Dickson, Saskia Schwarzer, Slade O. Jensen, and Lawrence A. Lavery. "Metatranscriptome sequencing identifies Escherichia are major contributors to pathogenic functions and biofilm formation in diabetes related foot osteomyelitis." Frontiers in Microbiology 13 (August 1, 2022). http://dx.doi.org/10.3389/fmicb.2022.956332.

Full text

Abstract:

Osteomyelitis in the feet of persons with diabetes is clinically challenging and is associated with high rates of amputation. In this study RNA-sequencing was employed to explore microbial metatranscriptomes with a view to understand the relative activity and functions of the pathogen/s responsible for diabetes foot osteomyelitis (DFO). We obtained 25 intraoperative bone specimens from persons with confirmed DFO, observing that Escherichia spp. (7%), Streptomyces spp. (7%), Staphylococcus spp. (6%), Klebsiella spp. (5%) and Proteus spp. (5%) are the most active taxa on average. Data was then subset to examine functions associated with pathogenesis (virulence and toxins), biofilm formation and antimicrobial/multi-drug resistance. Analysis revealed Escherichia spp. are the most active taxa relative to pathogenic functions with K06218 (mRNA interferase relE), K03699 (membrane damaging toxin tlyC) and K03980 (putative peptidoglycan lipid II flippase murJ), K01114 (membrane damaging toxin plc) and K19168 (toxin cptA) being the most prevalent pathogenic associated transcripts. The most abundant transcripts associated with biofilm pathways included components of the biofilm EPS matrix including glycogen synthesis, cellulose synthesis, colonic acid synthesis and flagella synthesis. We further observed enrichment of a key enzyme involved in the biosynthesis of L-rhamnose (K01710 -dTDP-glucose 4,6-dehydratase rfbB, rmlB, rffG) which was present in all but four patients with DFO.

APA, Harvard, Vancouver, ISO, and other styles

47

Krones, David, Marcel Rühling, Katrin Anne Becker, Tobias C. Kunz, Carolin Sehl, Kerstin Paprotka, Erich Gulbins, and Martin Fraunholz. "Staphylococcus aureus α-Toxin Induces Acid Sphingomyelinase Release From a Human Endothelial Cell Line." Frontiers in Microbiology 12 (July 29, 2021). http://dx.doi.org/10.3389/fmicb.2021.694489.

Full text

Abstract:

Staphylococcus aureus (S. aureus) is well known to express a plethora of toxins of which the pore-forming hemolysin A (α-toxin) is the best-studied cytolysin. Pore-forming toxins (PFT) permeabilize host membranes during infection thereby causing concentration-dependent effects in host cell membranes ranging from disordered ion fluxes to cytolysis. Host cells possess defense mechanisms against PFT attack, resulting in endocytosis of the breached membrane area and delivery of repair vesicles to the insulted plasma membrane as well as a concurrent release of membrane repair enzymes. Since PFTs from several pathogens have been shown to recruit membrane repair components, we here investigated whether staphylococcal α-toxin is able to induce these mechanisms in endothelial cells. We show that S. aureus α-toxin induced increase in cytosolic Ca2+ in endothelial cells, which was accompanied by p38 MAPK phosphorylation. Toxin challenge led to increased endocytosis of an extracellular fluid phase marker as well as increased externalization of LAMP1-positive membranes suggesting that peripheral lysosomes are recruited to the insulted plasma membrane. We further observed that thereby the lysosomal protein acid sphingomyelinase (ASM) was released into the cell culture medium. Thus, our results show that staphylococcal α-toxin triggers mechanisms in endothelial cells, which have been implicated in membrane repair after damage of other cell types by different toxins.

APA, Harvard, Vancouver, ISO, and other styles

48

Lata, Kusum, Mahendra Singh, Shamaita Chatterjee, and Kausik Chattopadhyay. "Membrane Dynamics and Remodelling in Response to the Action of the Membrane-Damaging Pore-Forming Toxins." Journal of Membrane Biology, March 19, 2022. http://dx.doi.org/10.1007/s00232-022-00227-z.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Dombach, Jamie L., Joaquin L. J. Quintana, and Corrella S. Detweiler. "Staphylococcal Bacterial Persister Cells, Biofilms, and Intracellular Infection Are Disrupted by JD1, a Membrane-Damaging Small Molecule." mBio 12, no. 5 (October 26, 2021). http://dx.doi.org/10.1128/mbio.01801-21.

Full text

Abstract:

Untreatable bacterial infections are a critical public health care issue. In addition to increasing antibiotic resistance, bacteria that are in slow-growing or nongrowing states, or that live inside mammalian cells, are typically insensitive to clinical antibiotics and therefore difficult to eradicate.

APA, Harvard, Vancouver, ISO, and other styles

50

Le, Vien T. M., Hoan N. Le, Marcos Gabriel Pinheiro, Kenneth J. Hahn, Mary L. Dinh, Kajal B. Larson, Shawn D. Flanagan, et al. "Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia." Antimicrobial Agents and Chemotherapy 61, no. 4 (January 30, 2017). http://dx.doi.org/10.1128/aac.02734-16.

Full text

Abstract:

ABSTRACT The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily (P = 0.003) and 17% for rabbits treated with saline (P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus-secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Staphylococcal membrane damaging toxins'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles