DltABCD-mediated d-alanylation of teichoic acids in Group A Streptococcus confers innate immune resistance

Abstract

Group A Streptococcus (GAS) is a major cause of both mucosal and invasive human infections. Epithelial and leukocyte production of cationic antimicrobial peptides (AMPs) is an important aspect of mammalian innate immune defense against bacterial infection. In this study, we identify a specific GAS phenotype that confers resistance to host AMPs. Inactivation of the dltA gene in an invasive serotype M1 GAS isolate led to loss of teichoic acid d-alanylation. Compared to the wild-type strain, the GAS dltA mutant was found to be more susceptible to AMP and lysozyme killing. Killing of the dltA mutant by human PMN, which produce AMPs in large amounts, was greatly accelerated. Thus, teichoic acid d-alanylation may contribute to the ability of invasive GAS to bypass mucosal defenses and produce systemic infection.