The capsular polysaccharide obstructs wall teichoic acid functions in Staphylococcus aureus

J Infect Dis. 2024 May 14:jiae188. doi: 10.1093/infdis/jiae188. Online ahead of print.

Abstract

Background: The cell envelope of Staphylococcus aureus contains two major secondary cell wall glycopolymers: capsular polysaccharide (CP) and wall teichoic acid (WTA). Both the CP and the WTA are attached to the cell wall and play distinct roles in S. aureus colonization, pathogenesis, and bacterial evasion of host immune defenses.

Objective: We aimed to investigate whether CP interferes with WTA-mediated properties.

Methods: Strains with natural heterogeneous expression of CP, strains with homogeneous high CP expression and CP-deficient strains were compared to WTA deficient controls regarding WTA dependent phage binding, cell adhesion, IgG deposition, and virulence in vivo.

Results: WTA-mediated phage adsorption, specific antibody deposition and cell adhesion were negatively correlated with CP expression. WTA, but not CP, enhanced the bacterial burden in a mouse abscess model, while CP overexpression resulted in intermediate virulence in vivo.

Conclusions: CP protects the bacteria from WTA-dependent opsonization and phage binding. This protection comes at the cost of diminished adhesion to host cells. The highly complex regulation and mostly heterogeneous expression of CP has probably evolved to ensure the survival and optimal physiological adaptation of the bacterial population as a whole.

Keywords: Staphylococcus; WTA; abscess; capsule; cell wall; phage; polysaccharide; virulence.