Staphylococcal exfoliative toxins: “Molecular scissors” of bacteria that attack the cutaneous defense barrier in mammals

Nishifuji, Koji; Sugai, Motoyuki; Amagai, Masayuki

doi:10.1016/j.jdermsci.2007.05.007

Cited by 136 publications

(115 citation statements)

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“…SEC and TSST-1 modulate adaptive responses by non-antigen-directed binding of major histocompatibility complex (MHC) class II with T cell receptors, resulting in polyclonal T cell activation (60). Neutrophils are targeted by the ␥-hemolysin family (HlgB and LukD, -E, -F, and -S) (20), desmosomes are targeted by exfoliative toxins (ETA and -B) (61), and alpha-toxin lyses mononuclear immune cells and platelets (62). SSL9 binds to monocytes and dendritic cells and blocks the complement system (63,64), and no clear function has thus far been described for SSL1.…”

Section: Discussionmentioning

confidence: 99%

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

et al. 2015

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f IgG4 responses are considered indicative for long-term or repeated exposure to particular antigens. Therefore, studying IgG4-specific antibody responses against Staphylococcus aureus might generate new insights into the respective host-pathogen interactions and the microbial virulence factors involved. Using a bead-based flow cytometry assay, we determined total IgG (IgGt), IgG1, and IgG4 antibody responses to 40 different S. aureus virulence factors in sera from healthy persistent nasal carriers, healthy persistent noncarriers, and patients with various staphylococcal infections from three distinct countries. IgGt responses were detected against all tested antigens. These were mostly IgG1 responses. In contrast, IgG4 antibodies were detected to alphatoxin, chemotaxis inhibitory protein of S. aureus (CHIPS), exfoliative toxins A and B (ETA and -B), HlgB, IsdA, LukD, -E, -F, and -S, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin C (SEC), staphylococcal superantigen-like proteins 1, 3, 5, and 9 (SSL1, -3, -5, and -9), and toxic shock syndrome toxin 1 (TSST-1) only. Large interpatient variability was observed, and the type of infection or geographical location did not reveal conserved patterns of response. As persistent S. aureus carriers trended toward IgG4 responses to a larger number of antigens than persistent noncarriers, we also investigated sera from patients with epidermolysis bullosa (EB), a genetic blistering disease associated with high S. aureus carriage rates. EB patients responded immunologically to significantly more antigens than noncarriers and trended toward even more responses than carriers. Altogether, we conclude that the IgG4 responses against a restricted panel of staphylococcal antigens consisting primarily of immune modulators and particular toxins indicate important roles for these virulence factors in staphylococcal pathogen-host interactions, such as chronicity of colonization and/or (subclinical) infections.

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Section: Discussionmentioning

confidence: 99%

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

et al. 2015

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“…They have glutamate-specific 9 serine protease activity and selectively cleave a single peptide bond in the extracellular 10 region of human and mouse desmoglein 1 (Dsg1; desmosomal intercellular adhesion 11 molecule), a keratinocyte cell-cell adhesion molecule. In this way, the ETs act as 12 "molecular scissors" facilitating bacterial skin invasion (Nishifuji, Sugai et al 2008). By shown that ~80% of S. aureus clinical isolates harbor an average of five to six SAg genes.…”

Section: Exfoliative Toxins (Ets)mentioning

confidence: 99%

Staphylococcus aureus toxins – Their functions and genetics

Grumann

Nübel

Bröker

2014

Infection, Genetics and Evolution

177

170

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“…S. aureus produces a wide range of virulence factors that mediate host colonization, invasion of damaged skin and mucosa, dissemination through the body, and evasion of host defense mechanisms (8,12). Relevant among them are a variety of exotoxins that comprise ␣-, ␤-, ␥-, and ␦-hemolysins, leukotoxins (the classical LukS-PV-LukF-PV Panton-Valentine leukocidin [LukPV], LukE-LukD [LukED] and LukM-LukFЈ-PV [LukM]), exfoliative toxins, and pyrogenic toxin superantigens, such as the staphylococcal TSS toxin (TSST-1, first referred to as SEF) and staphylococcal enterotoxins (SEs) (14,29,43). Five major serological types of SEs, SEA through SEE (known as classical enterotoxins, encoded by the sea to see genes, respectively) have been initially identified.…”

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Clonal Complexes and Diversity of Exotoxin Gene Profiles in Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Isolates from Patients in a Spanish Hospital

et al. 2009

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Molecular epidemiology studies have allowed the identification of the methicillin (meticillin)-resistant (MRSA) and methicillin-susceptible (MSSA) clonal complexes (CCs) and clones of, and CC59 were also detected. Many exotoxin genes were present in each of the 81 isolates, independent of whether they were involved in sepsis (11 to 22) or other types of infections (13 to 21), and they appeared in 73 combinations. The relevant data are that (i) all isolates were positive for hemolysin and leukotoxin genes (98.8% for lukED and 25.9% for lukPV); (ii) all contained an enterotoxin gene cluster (egc with or without seu), frequently with one or more genes encoding classical enterotoxins; (iii) about half were positive for tst and 95% were positive for exfoliatin-encoding genes (eta, etb, and/or etd); and (iv) the four agr groups were detected, with agrII (55.6%) and agrIII (23.5%) being the most frequent. Taken together, results of the present study suggest a frequent acquisition and/or loss of exotoxin genes, which may be mediated by efficient intralineage transfer of mobile genetic elements and exotoxin genes therein and by eventual breakage of interlineage barriers.Staphylococcus aureus is both a commensal bacterium and an extremely versatile pathogen that causes a wide range of diseases in humans, including superficial, deep-seated, and systemic infections, as well as a variety of toxemic syndromes, such as toxic shock syndrome (TSS), staphylococcal scaldedskin syndrome (SSSS), and staphylococcal food poisoning (36). S. aureus produces a wide range of virulence factors that mediate host colonization, invasion of damaged skin and mucosa, dissemination through the body, and evasion of host defense mechanisms (8,12). Relevant among them are a variety of exotoxins that comprise ␣-, ␤-, ␥-, and ␦-hemolysins, leukotoxins (the classical LukS-PV-LukF-PV Panton-Valentine leukocidin [LukPV], LukE-LukD [LukED] and LukM-LukFЈ-PV [LukM]), exfoliative toxins, and pyrogenic toxin superantigens, such as the staphylococcal TSS toxin (TSST-1, first referred to as SEF) and staphylococcal enterotoxins (SEs) (14,29,43). Five major serological types of SEs, SEA through SEE (known as classical enterotoxins, encoded by the sea to see genes, respectively) have been initially identified. However, new types of SEs and their coding genes (seg through seu) were later reported. Several SE genes (seg, sei, sem, sen, and seo) are part of an operon termed the enterotoxin gene cluster (egc

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Staphylococcal exfoliative toxins: “Molecular scissors” of bacteria that attack the cutaneous defense barrier in mammals

Cited by 136 publications

References 50 publications

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

IgG4 Subclass-Specific Responses to Staphylococcus aureus Antigens Shed New Light on Host-Pathogen Interaction

Staphylococcus aureus toxins – Their functions and genetics

Clonal Complexes and Diversity of Exotoxin Gene Profiles in Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Isolates from Patients in a Spanish Hospital

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