Abstract
AbstractCell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. These structures have also gained interest as vaccine antigens, in particular for the human pathogens Group AStreptococcus(GAS) andStreptococcus mutans. Streptococcal cell wall glycopolymers are considered to be functional homologues of wall teichoic acids but surprisingly lack the biologically-relevant and characteristic anionic charge. Here we identifygacH, a gene of unknown function in the GAS Group A Carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA secreted phospholipase A2. To understand the underlying mechanism of these phenotypes, we determined the structure of the extracellular domain of GacH and discover that it represents a new family of glycerol phosphate (GroP) transferases. Importantly, we demonstrate the presence of GroP in both the GAC and the homologous SerotypecCarbohydrate (SCC) fromS. mutans,which is conferred bygacHandsccHproducts, respectively. NMR analysis of GAC released from cell wall by non-destructive methods reveals that approximately 30% of the GAC GlcNAc side-chains are modified by GroP at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.Graphical abstract
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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1. Influence of Cell Wall Polysaccharides on Structure and Mechanics of Streptococcus mutans;Mechanics of Biological Systems and Materials & Micro-and Nanomechanics, Volume 4;2019-11-10