Abstract
Group A Streptococcus (GAS) is a gram‐positive bacterium that ranks within the top 10 of human pathogens responsible for mortalities every year. The human innate immune system combats and kills GAS through the enlistment of macrophages and neutrophils. Neutrophils can kill bacteria intracellularly via the generation of reactive oxygen species and release of antimicrobial granule contents. These molecules also contribute to a specific mechanism of neutrophil death, resulting in the production of neutrophil extracellular traps (NETs), which can kill bacteria extracellularly. We have shown that the GAS virulence factor Streptococcal collagen‐like protein (Scl‐1) increases bacterial survival in NETs while simultaneously lowering the overall production of NETs. In this work, we are exploring the mechanism by which Scl‐1 prevents NET formation, specifically investigating whether Scl‐1 decreases the production, activity or availability of antimicrobial factors that eventually lead to the formation of NETs. While the release of granules were not significantly different between cells infected with strains expressing or lacking Scl‐1, the content of the granules was shown to be an important factor in Scl‐1 mediated GAS survival. The antimicrobial peptide LL‐37 is released by the granules and subsequently aids in direct bacterial killing and NET formation. We found that Scl‐1 mediates protection against LL‐37 mediated bacterial killing in vitro. Transmission electron microscopy (TEM) imaging of bacteria within phagocytic cells indicates that strains expressing Scl‐1 are more intact, further supporting the idea that Scl‐1 is protective against LL‐37. We are currently exploring whether there is a linkage between LL‐37 activity within the phagocytic cells and extracellular trap formation. Our results shape our understanding of not only Scl‐1 prevention of NET formation, but also the general mechanism of NET generation in phagocytic cells.
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