The resurgence of Group A Streptococcus (GAS) infections in the past two decades has been a rising major public health concern. Due to a large number of GAS infections occurring in the skin, mast cells (MCs), innate immune cells known to localize to the dermis, could play an important role in controlling infection. MCs can exert their antimicrobial activities either early during infection, by degranulation and release of antimicrobial proteases and the cathelicidin-derived antimicrobial peptide LL-37, or by forming antibacterial MC extracellular traps (MCETs) in later stages of infection. We demonstrate that MCs do not directly degranulate in response to GAS, reducing their ability to control bacterial growth in early stages of infection. However, MC granule components are highly cytotoxic to GAS due to the pore-forming activity of LL-37, while MC granule proteases do not significantly affect GAS viability. We therefore confirmed the importance of MCETs by demonstrating their capacity to reduce GAS survival. The data therefore suggests that LL-37 from MC granules become embedded in MCETs, and are the primary effector molecule by which MCs control GAS infection. Our work underscores the importance of a non-traditional immune effector cell, utilizing a non-conventional mechanism, in the defense against an important human pathogen.

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.