d-Alanylation of Teichoic Acids Promotes Group A Streptococcus Antimicrobial Peptide Resistance, Neutrophil Survival, and Epithelial Cell Invasion

摘要: Group A streptococcus (GAS) is a leading cause of severe, invasive human infections, including necrotizing fasciitis and toxic shock syndrome. An important element the mammalian innate defense system against bacterial infections such as GAS production antimicrobial peptides (AMPs) cathelicidins. In this study, we identify specific phenotype that confers resistance to host AMPs. Allelic replacement dltA gene encoding d-alanine-d-alanyl carrier protein ligase in an serotype M1 isolate led loss teichoic acid d-alanylation increase net negative charge on surface. Compared wild-type (WT) parent strain, ΔdltA mutant exhibited increased susceptibility AMP lysozyme killing acidic pH. While phagocytic uptake WT mutants by neutrophils was equivalent, neutrophil-mediated strain greatly accelerated. Furthermore, observed be diminished its ability adhere invade cultured pharyngeal epithelial cells, likely proximal step pathogenesis infection. Thus, may contribute multiple ways propensity bypass mucosal defenses produce systemic