Wall Teichoic Acid Glycosylation of Staphylococcus epidermidis and the Interaction of Staphylococci with the Human Host

Abstract

Staphylococcus epidermidis colonizes the human skin microbiome of healthy individuals, but due to its ability to produce biofilms and to acquire antibiotic resistances, it can become an opportunistic pathogen and a frequent cause of foreign body related infections (FBRIs). As for most coagulase-negative Staphylococci (CoNS), S. epidermidis wall teichoic acid is composed of a long chain of glycerol-phosphate (GroP) repeating units linked to the cell wall peptidoglycan. While Staphylococcus aureus ribitol-phospate (RboP) wall teichoic acid (WTA) is glycosylated with n-acetylglucosamine (GlcNAc) and was shown to be involved in several cellular functions, including cell separation, binding to endothelial cells and immune activation, the composition and function of GroP-WTA is less well understood. We analyzed the WTA of S. epidermidis in detail and confirmed that GroP-WTA of S. epidermidis is mainly glycosylated with glucose by an enzyme with similarity to Bacillus subtilis TagE. This glucose residue determines the binding pattern of different types of bacteriophages, increasing adsorption of siphoviruses, while decreasing adsorption of podoviruses to the S. epidermidis host. We demonstrate that the presence of tagE in different CoNS determines horizontal gene transfer by Rockefellervirus ΦE72 and show that rare expression of S. aureus type RboP-WTA in S. epidermidis sequence type (ST) 23 can prevent binding of this phage. Additionally, we show that this RboP-WTA in S. epidermidis ST23 is also glycosylated with glucose by the enzyme TarM(S.e.) in a processive manner. As opposed to glycosylation with GlcNAc, glucose modified RboP-WTA shows reduced binding of human IgG and helps S. epidermidis to evade the immune system. Priming of neutrophils with acetate via the GPR43 receptor increases the immune response and inhibition of the ATP synthase sensitizes S. aureus towards antimicrobial peptides expressed by neutrophils and keratinocytes. Additionally, S. aureus releases pro-inflammatory membrane vesicles containing phenol soluble modulins (PSMs) and lipoproteins, which can activate formyl peptide receptors (FPRs) and toll-like receptors (TLRs), leading to increased neutrophil phagocytosis and cytokine release. Wall teichoic acid modulates the immune response as an important antigen and is the only described receptor for staphylococcal bacteriophages employed in phage therapy approaches. Understanding the wall teichoic acid of all potentially pathogenic CoNS is essential for treatment of infections with drug resistant Staphylococci.