Group A Streptococcus causes a spectrum of diseases ranging from pharyngitis to life‐threatening diseases such as streptococcal toxic shock‐like syndrome. Invasive strains of GAS increase the expression of virulence factors that promote bacterial survival in the face of the human immune system. One such virulence factor is Scl‐1, a surface collagen‐like protein that has been shown in other less virulent strains to mediate attachment and resistance to serum factors. Previous work in our lab demonstrated that Scl‐1 plays a role in bacterial survival against phagocytes, but the molecular mechanism for this enhanced survival has not been determined. In the current work, we determined that the presence of Scl‐1 promotes resistance to phagocytic antimicrobial factors such as peroxide. We then used transmission electron microscopy (TEM) to examine whether Scl‐1 can act as a physical barrier to antimicrobial molecules. Preliminary analysis of wild‐type, scl‐1 mutant, and plasmid‐complemented strains suggests differences in the cell wall density of the scl‐1 mutant strain. TEM analysis of peroxide‐treated strains also suggests that Scl‐1 provides a physical barrier to protect the bacterial membrane from oxidative damage. Thus, Scl‐1 contributes to the virulence of the bacteria by acting as a molecular “shield” to protect the bacteria from antimicrobial molecules produced by phagocytic cells.

The up‐regulation of the gene encoding Streptococcal collagen‐like protein (scl‐1) in invasive Group A Streptococcus has been hypothesized to promote bacterial resistance to host defenses. Our previous data demonstrated that when incubated with phagocytic cells, an scl‐1 mutant strain exhibits significantly decreased survival compared to wild‐type and plasmid‐complemented strains. In our current study, we have collected results that support two possible molecular mechanisms by which Scl‐1 contributes to bacterial evasion of phagocytic killing. First, the surface protein Scl‐1 may serve as a physical barrier to mediate resistance to antimicrobial molecules contained in phagocytic cell granules. Scl‐1 directly contributes to bacterial resistance to the antimicrobial peptide human cathelicidin LL‐37, granule proteases and reactive oxygen species, though Scl‐1 does not affect peroxide production by phagocytic cells per se. Secondly, Scl‐1 contributes to bacterial survival by suppression of degranulation and release of antimicrobial molecules, and consequently the formation of neutrophil extracellular traps (NETs). Thus, the results show that Scl‐1 is a multi‐faceted virulence factor that mediates bacterial evasion to phagocytic killing by both suppressing the host response and by mediating direct resistance to antimicrobial molecules.