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Review
. 2019;11(1):3-12.
doi: 10.1159/000492944. Epub 2018 Sep 28.

Catch Me if You Can: Streptococcus Pyogenes Complement Evasion Strategies

Free PMC article
Review

Catch Me if You Can: Streptococcus Pyogenes Complement Evasion Strategies

Maisem Laabei et al. J Innate Immun. .
Free PMC article

Abstract

The human host has evolved elaborate protection mechanisms to prevent infection from the billions of microorganisms to which it host is exposed and is home. One of these systems, complement, is an evolutionary ancient arm of innate immunity essential for combatting bacterial infection. Complement permits the efficient labelling of bacteria with opsonins, supports phagocytosis, and facilitates phagocyte recruitment to the site of infection through the production of chemoattractants. However, it is by no means perfect, and certain organisms engage in an evolutionary arms race with the host where complement has become a major target to promote immune evasion. Streptococcus pyogenes is a major human pathogen that causes significant morbidity and mortality globally. S. pyogenes is also a member of an elite group of bacterial pathogens possessing a sophisticated arsenal of virulence determinants capable of interfering with complement. In this review, we focus on these complement evasins, their mechanism of action, and their importance in disease progression. Finally, we highlight new therapeutic options for fighting S. pyogenes, by interfering with one of its main mechanisms of complement evasion.

Keywords: Complement; Immune evasion; Innate immunity; M protein; Pathogenicity; Streptococcus pyogenes.

Figures

Fig. 1
Fig. 1
Surface-bound S. pyogenes evasins. Schematic representation of how surface-bound bacterial virulence factors interact with human serum proteins. Inhibition or degradation is indicated by red lines. Host proteins that interact with S. pyogenes are written in black, while bacterial virulence factors are written in blue (accompanied by a number from 1 to 8). The M protein family (1) consists of M protein and proteins Enn, Arp, Sir, Mrp, and H (listed in online suppl. Table 1). Despite the capsule (5) not being a defined single molecule, it is an important factor contributing significantly to virulence. GAPDH (6) is not a traditional surface protein but is bound to the surface and depletes C5a there. Vitronectin-binding protein (8) has not been described as affecting complement, but vitronectin itself is known to inhibit MAC formation; to highlight this, a question mark was added to the schema. CP, classical pathway; LP, lectin pathway; AP, alternative pathway.
Fig. 2
Fig. 2
Secreted virulence factors of S. pyogenes. Schematic representation of how secreted virulence determinants (written in blue and accompanied by a letter of the alphabet from A to H) interfere with complement activity. Inhibition or degradation is indicated by red lines. The effect of SpeB on IgG is not entirely clear, and so is indicated with a question mark. Similarly, the effect of streptokinase on plasminogen conversion to plasmin at the bacterial surface and how this modifies C3b is currently under debate. CP, classical pathway; LP, lectin pathway; AP, alternative pathway.

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