<i>Staphylococcus aureus</i>Secreted Toxins and Extracellular Enzymes

Tam, Kayan; Torres, Victor J.

doi:10.1128/9781683670131.ch40

Cited by 41 publications

(53 citation statements)

References 346 publications

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“…S. aureus expresses leukocidins and phenol-soluble modulins that target DCs, inhibiting antigen uptake, presentation, and T cell proliferation (27,28). As species-specific cellular receptors define the activity of multiple staphylococcal toxins (29), our observations of the role of Hla in modulating the murine antigen-specific T cell response suggest that this response may also be modified in humans through the combined cellular action of toxins. S. aureus may thus rely on multiple virulence factors in skin infection to simultaneously cause injury and manipulate host immunity.…”

Section: Resultsmentioning

confidence: 91%

Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Lee¹,

Olaniyi²,

Kwieciński³

et al. 2020

Journal of Clinical Investigation

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Section: Resultsmentioning

confidence: 91%

Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Lee¹,

Olaniyi²,

Kwieciński³

et al. 2020

Journal of Clinical Investigation

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“…Receptors for several β-PFTs have recently been identified, however, the exact molecular interactions between the secreted toxins and the receptor proteins still remain elusive (Rumah et al, 2015;Shrestha and McClane, 2013;Spaan et al, 2017;Tam and Torres, 2019). Here we demonstrate that CPB toxicity specifically requires the Ig6 domain of CD31.…”

Section: Discussionmentioning

confidence: 73%

“…For a long time, membrane lipids were thought to function as receptors for most PFTs, however this could not sufficiently explain the cell-type and species-specificity of many of these toxins (DuMont and Torres, 2014;Peraro and van der Goot, 2016). Recently several protein receptors for important PFTs have been identified, opening new opportunities for research on the pathogenesis and therapy of bacterial infections (Rumah et al, 2015;Shrestha and McClane, 2013;Spaan et al, 2017;Tam and Torres, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to S. aureus, which affects a wide range of different organ systems using up to 8 currently known small pore-forming β-PFTs (Tam and Torres, 2019), C. perfringens type C seems to utilize mainly CPB to cause vascular damage in the intestine of susceptible hosts (Sayeed et al, 2008). We previously provided evidence that CPB primarily targets endothelial cells in the small intestinal mucosa in vivo (Miclard et al, 2009a;Miclard et al, 2009b;Schumacher et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Cell-specific targeting byClostridium perfringensβ-toxin unraveled: the role of CD31 as the toxin receptor

Bruggisser

Tarek

Wyder

et al. 2019

Preprint

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Clostridium perfringens β-toxin (CPB) is a highly active hemolysin β-pore forming toxin and the essential virulence factor for a severe, necro-hemorrhagic enteritis in animals and humans. In vivo and in vitro it exerts a remarkable cell type specificity towards endothelial cells, platelets and some leucocytic cell lines. The target cell specificity of CPB is, however, poorly understood and a receptor explaining this selective toxicity has not been identified. This has hampered further research into the pathogenesis of C. perfringens type C induced enteritis. Here we identify Platelet Endothelial Cell Adhesion Molecule-1 (CD31 or PECAM-1) as the specific membrane receptor for CPB on endothelial cells. CD31 expression is essential for CPB toxicity in endothelial cells and lethality in mice and sufficient to render previously resistant cells highly susceptible to the toxin. We further demonstrate, that the extracellular membrane proximal Ig6 domain of CD31 is required for the interaction with CPB and that expression of CD31 corresponds with the specificity of the toxin towards cultured cell lines. Our results thus provide an explanation for the cell type specificity of CPB and can be linked to the characteristic lesions observed a devastating enteric disease in animals and humans.

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“…This approach has enabled the identification and characterisation of many of the proteins used by S. aureus to cause disease, and some of the complex means by which it regulates the expression of these proteins. For example, the secretion of toxins such as alpha-toxin 6,7 and the phenol-soluble modulins (PSMs) 7,8 has been associated with increased virulence; and nearly all toxins are under the control of a two-component, quorum sensing system called the accessory gene regulator (Agr) 9,10 . However, many additional regulatory systems also contribute to S. aureus virulence e.g.…”

Section: Introductionmentioning

confidence: 99%

A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus

Duggan

Laabei

Al-Nahari

et al. 2019

Preprint

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Staphylococcus aureus is a major human pathogen, where the widespread emergence of antibiotic resistance is making infections more challenging to treat. Toxin induced tissue damage and resistance to the host’s immune system are well established as critical to its ability to cause disease. However, recent attempts to study S. aureus pathogenicity at a population level have revealed significant complexity and hierarchical levels of regulation. In an effort to better understand this we have identified and characterized a principle effector protein, MasA. The inactivation of this small highly-conserved membrane protein simultaneously disrupts toxin production and impairs S. aureus’ ability to resist several aspects of the innate immune system. These pleiotropic effects are mediated by both a change in the stability of the bacterial membrane and the dysregulation of iron homeostasis, which results in a significant impairment in the ability of S. aureus to cause infection in both a subcutaneous and a sepsis model of infection. That proteins with such major effects on pathogenicity remain unidentified in a bacterium as well studied as S. aureus demonstrates how incomplete our understanding of their ability to cause disease is, an issue that needs to be addressed if effective control and treatment strategies are to be developed.

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Staphylococcus aureusSecreted Toxins and Extracellular Enzymes

Cited by 41 publications

References 346 publications

Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Staphylococcus aureus toxin suppresses antigen-specific T cell responses

Cell-specific targeting byClostridium perfringensβ-toxin unraveled: the role of CD31 as the toxin receptor

A small membrane protein critical to both the offensive and defensive capabilities of Staphylococcus aureus

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