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Review
. 2019 Jun 11;11(6):332.
doi: 10.3390/toxins11060332.

The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections

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Free PMC article
Review

The Role of Streptococcal and Staphylococcal Exotoxins and Proteases in Human Necrotizing Soft Tissue Infections

Patience Shumba et al. Toxins (Basel). .
Free PMC article

Abstract

Necrotizing soft tissue infections (NSTIs) are critical clinical conditions characterized by extensive necrosis of any layer of the soft tissue and systemic toxicity. Group A streptococci (GAS) and Staphylococcus aureus are two major pathogens associated with monomicrobial NSTIs. In the tissue environment, both Gram-positive bacteria secrete a variety of molecules, including pore-forming exotoxins, superantigens, and proteases with cytolytic and immunomodulatory functions. The present review summarizes the current knowledge about streptococcal and staphylococcal toxins in NSTIs with a special focus on their contribution to disease progression, tissue pathology, and immune evasion strategies.

Keywords: Staphylococcus aureus; Streptococcus pyogenes; group A streptococcus; immune responses; immunomodulatory proteases; necrotizing soft tissue infections; pore-forming toxins; skin infections; superantigens.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Streptococcal and staphylococcal secreted virulence factors with pore-forming and/or immunomodulatory properties. (a) Group A streptococcal (GAS) secreted factors: Streptolysins S and O (SLS, SLO), streptococcal pyrogenic exotoxin B (SpeB), superantigens (SAgs), C5a peptidase (ScpA), Immunoglobulin degrading enzyme of streptococci (IdeS), SpyCEP, SpyA, Streptokinase (Ska), and NADase. (b) Staphylococcal secreted factors: Leukocidins, α-toxin, phenol-soluble modulins (PSMs), superantigens (SAgs), staphopain A (ScpA), Staphopain B (SspB), Aureolysin (Aur), V8 protease, exfoliative toxins (ETs), epidermin leader processing protease (EpiP), serine protease-like proteins (Spls), and staphylokinase (SAK).
Figure 2
Figure 2
Superantigen (SAg) driven T cell activation. (a) Antigen presenting cell (APC) presents a processed antigen peptide on the MHC class II molecule to a T cell via T cell receptor. A process called conventional antigen presentation. (b) SAgs bind without cellular processing to MHC class II molecule and variable beta (Vβ) chain on the T cell receptor. This results in uncontrolled T cell activation.
Figure 3
Figure 3
Streptolysin S (SLS) mediated tissue pathology. Group A streptococci (GAS) translocate through the epithelium via cleavage of the junction proteins or direct damage. Once deeper layers are reached SLS stimulates neurons to release calcitonin gene-related protein (CGRP), which inhibits the recruitment of neutrophils. In addition, direct damage of neutrophils, monocytes, and macrophages impairs phagocytic clearance of the bacteria and contributes further to tissue damage. Failed clearance of the pathogen results bacterial dissemination and biofilm formation.

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