Alpha-toxin of Staphylococcus aureus.

Bhakdi, Sucharit; Tranum‐Jensen, Jørgen

doi:10.1128/mmbr.55.4.733-751.1991

Cited by 517 publications

(332 citation statements)

References 109 publications

(195 reference statements)

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“…6A). Consistent with this finding, we noted that a-haemolysin from Staphylococcus aureus, a pore-forming toxin structurally unrelated to pneumolysin (Bhakdi and Tranum-Jensen, 1991), and anthrolysin O from Bacillus anthracis, which like pneumolysin is a cholesterol-dependent cytolysin (Shannon et al, 2003), also led to synergistic enhancement of FK156-induced NFkB activation (Fig. 6B).…”

Section: The Pore-forming Property Of Pneumolysin Accounts For Its Cosupporting

confidence: 83%

Nod1 mediates cytoplasmic sensing of combinations of extracellular bacteria

Ratner¹,

Aguilar

Shchepetov

et al. 2007

Cell Microbiol

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SummaryDuring mucosal colonization, epithelial cells are concurrently exposed to numerous microbial species. Epithelial cytokine production is an early component of innate immunity and contributes to mucosal defence. We have previously demonstrated a synergistic response of respiratory epithelial cells to costimulation by two human pathogens, Streptococcus pneumoniae and Haemophilus influenzae. Here we define a molecular mechanism for the synergistic activation of epithelial signalling during polymicrobial colonization. H. influenzae peptidoglycan synergizes with the pore-forming toxin pneumolysin from S. pneumoniae. Radiolabelled peptidoglycan enters epithelial cells more efficiently in the presence of pneumolysin, consistent with peptidoglycan gaining access to the cytoplasm via toxin pores. Other poreforming toxins (including anthrolysin O from Bacillus anthracis and Staphylococcus aureus a-toxin) can substitute for pneumolysin in the generation of synergistic responses. Consistent with a requirement for pore formation, S. pneumoniae expressing pneumolysin but not an isogenic mutant expressing a nonpore-forming toxoid prime epithelial responses. Nod1, a host cytoplasmic peptidoglycan-recognition molecule, is crucial to the epithelial response. Taken together, these findings demonstrate a role for cytosolic recognition of peptidoglycan in the setting of polymicrobial epithelial stimulation. We conclude that combinations of extracellular organisms can activate innate immune pathways previously considered to be reserved for the detection of intracellular microorganisms.

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Section: The Pore-forming Property Of Pneumolysin Accounts For Its Cosupporting

confidence: 83%

Nod1 mediates cytoplasmic sensing of combinations of extracellular bacteria

Ratner¹,

Aguilar

Shchepetov

et al. 2007

Cell Microbiol

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“…The fact that an antimicrobial treatment results in an improvement of eczema in AD patients who are colonized with S. aureus strains unable to produce superantigens [10] suggests that other factors than superantigens derived from S. aureus may contribute to the development and maintenance of the eczema. S. aureus a-toxin (a-hemolysin), a cytolysin which does not belong to the group of enterotoxins (superantigens) is produced by a high percentage of human S. aureus isolates [19,31]. We detected a-toxin producing S. aureus strains on the skin of more than 30% of our adult patients with AD, who exhibited no overt evidence of cutaneous infection.…”

Section: Discussionmentioning

confidence: 84%

Alpha‐toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis

Breuer

Wittmann

Kempe

et al. 2005

Clin Experimental Allergy

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“…The results of the current study have shed some light on this issue because we found that S. aureus strongly enhanced the expression of β1 integrin in MCs. Furthermore, we demonstrated that the up-regulation of β1 integrin in MCs was mediated by the staphylococcal Hla, a pore-forming toxin released by most S. aureus clinical strains (Bhakdi and Tranum-Jensen, 1991). Hla has emerged as an important virulence factor contributing to the pathogenesis of S. aureus infections (Bubeck Wardenburg et al, 2007;Inoshima et al, 2011;Powers et al, 2012).…”

Section: Discussionmentioning

confidence: 92%

“…An intriguing question was how Hla upregulated the expression of β1 integrin in MCs. At high concentrations, Hla can cause pore formation leading to cells death (Bhakdi and Tranum-Jensen, 1991;Bantel et al, 2001;Essmann et al, 2003). However, at low concentrations, Hla can modulate key host signalling pathways, including those essential to the host inflammatory responses (Rose et al, 2002;Onogawa, 2002;Craven et al, 2009;Kebaier et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

α-Hemolysin enhancesStaphylococcus aureusinternalization and survival within mast cells by modulating the expression of β1 integrin

Goldmann

Tuchscherr

Rohde

et al. 2016

Cellular Microbiology

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Mast cells (MCs) are important sentinels of the host defence against invading pathogens. We previously reported that Staphylococcus aureus evaded the extracellular antimicrobial activities of MCs by promoting its internalization within these cells via β1 integrins. Here, we investigated the molecular mechanisms governing this process. We found that S. aureus responded to the antimicrobial mediators released by MCs by up-regulating the expression of α-hemolysin (Hla), fibronectin-binding protein A and several regulatory systems. We also found that S. aureus induced the up-regulation of β1 integrin expression on MCs and that this effect was mediated by Hla-ADAM10 (a disintegrin and metalloproteinase 10) interaction. Thus, deletion of Hla or inhibition of Hla-ADAM10 interaction significantly impaired S. aureus internalization within MCs. Furthermore, purified Hla but not the inactive HlaH35L induced up-regulation of β1 integrin expression in MCs in a dose-dependent manner. Our data support a model in which S. aureus counter-reacts the extracellular microbicidal mechanisms of MCs by increasing expression of fibronectin-binding proteins and by inducing Hla-ADAM10-mediated up-regulation of β1 integrin in MCs. The up-regulation of bacterial fibronectin-binding proteins, concomitantly with the increased expression of its receptor β1 integrin on the MCs, resulted in enhanced S. aureus internalization through the binding of fibronectin-binding proteins to integrin β1 via fibronectin.

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Alpha-toxin of Staphylococcus aureus.

Abstract: gene (120a). Both coagulase-positive and coagulase-negative staphylococci may produce other hemolysins, designated beta-, gamma-, and delta-toxins, that are molecularly distinct from alpha-toxin and whose roles as virulence factors 733

Cited by 517 publications

References 109 publications

Nod1 mediates cytoplasmic sensing of combinations of extracellular bacteria

Nod1 mediates cytoplasmic sensing of combinations of extracellular bacteria

Alpha‐toxin is produced by skin colonizing Staphylococcus aureus and induces a T helper type 1 response in atopic dermatitis

α-Hemolysin enhancesStaphylococcus aureusinternalization and survival within mast cells by modulating the expression of β1 integrin

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