An accessory wall teichoic acid glycosyltransferase protects Staphylococcus aureus from the lytic activity of Podoviridae.

Xuehua Li,David Gerlach,Andreas Peschel,Jesper Larsen,Marc Stegger,Xin Du,Guoqing Xia,Petra Kühner,Volker Winstel

doi:10.1038/srep17219

Abstract

Many Staphylococcus aureus have lost a major genetic barrier against phage infection, termed clustered regularly interspaced palindromic repeats (CRISPR/cas). Hence, S. aureus strains frequently exchange genetic material via phage-mediated horizontal gene transfer events, but, in turn, are vulnerable in particular to lytic phages. Here, a novel strategy of S. aureus is described, which protects S. aureus against the lytic activity of Podoviridae, a unique family of staphylococcal lytic phages with short, non-contractile tails. Unlike most staphylococcal phages, Podoviridae require a precise wall teichoic acid (WTA) glycosylation pattern for infection. Notably, TarM-mediated WTA α-O-GlcNAcylation prevents infection of Podoviridae while TarS-mediated WTA β-O-GlcNAcylation is required for S. aureus susceptibility to podoviruses. Tracking the evolution of TarM revealed an ancient origin in other staphylococci and vertical inheritance during S. aureus evolution. However, certain phylogenetic branches have lost tarM during evolution, which rendered them podovirus-susceptible. Accordingly, lack of tarM correlates with podovirus susceptibility and can be converted into a podovirus-resistant phenotype upon ectopic expression of tarM indicating that a “glyco-switch” of WTA O-GlcNAcylation can prevent the infection by certain staphylococcal phages. Since lytic staphylococcal phages are considered as anti-S. aureus agents, these data may help to establish valuable strategies for treatment of infections.

Highlights

Many Staphylococcus aureus have lost a major genetic barrier against phage infection, termed clustered regularly interspaced palindromic repeats (CRISPR/cas)
Even though some test strains were susceptible to Podoviridae, these phages seem to have a narrower host-range than other lytic staphylococcal phages
Podovirus-susceptible S. aureus strains were found among several clonal lineages suggesting that Podoviridae probably do not require an sequence type (ST)-specific receptor for adsorption and infection, as reported recently for the S. aureus ST395-specific phage Φ 18711,12 (Table 1)

Summary

Introduction

Many Staphylococcus aureus have lost a major genetic barrier against phage infection, termed clustered regularly interspaced palindromic repeats (CRISPR/cas). A novel strategy of S. aureus is described to prevent adsorption and infection of Podoviridae, a specific class of staphylococcal lytic phages with very short, non-contractile tails. Podovirus-susceptible S. aureus strains were found among several clonal lineages suggesting that Podoviridae probably do not require an ST-specific receptor for adsorption and infection, as reported recently for the S. aureus ST395-specific phage Φ 18711,12 (Table 1).

Results

Conclusion