Abstract
Despite the importance of phages in driving horizontal gene transfer (HGT) among pathogenic bacteria, the underlying molecular mechanisms mediating phage adsorption to S. aureus are still unclear. Phage ϕ11 is a siphovirus with a high transducing efficiency. Here, we show that the tail protein Gp45 localized within the ϕ11 baseplate. Phage ϕ11 was efficiently neutralized by anti-Gp45 serum, and its adsorption to host cells was inhibited by recombinant Gp45 in a dose-dependent manner. Flow cytometry analysis demonstrated that biotin-labelled Gp45 efficiently stained the wild-type S. aureus cell but not the double knockout mutant ΔtarM/S, which lacks both α- and β-O-GlcNAc residues on its wall teichoic acids (WTAs). Additionally, adsorption assays indicate that GlcNAc residues on WTAs and O-acetyl groups at the 6-position of muramic acid residues in peptidoglycan are essential components of the ϕ11 receptor. The elucidation of Gp45-involved molecular interactions not only broadens our understanding of siphovirus-mediated HGT, but also lays the groundwork for the development of sensitive affinity-based diagnostics and therapeutics for S. aureus infection.
Highlights
Host cell initially depends on the reversible binding to WTAs, which accelerates the subsequent irreversible binding to membrane receptor YueB8
We have shown that staphylococcal siphoviruses use α-O-GlcNAc modified WTA as a receptor[11] and that WTA structures govern phage-mediated horizontal transfer of S. aureus pathogenicity islands (SaPIs) among major bacterial pathogens[12]
The HHpred analysis identified Gp43 with 100% probability as a distal tail protein (Dit) because it is similar to the Dit protein (PDB 2 × 8K) in the baseplate of the siphophage SPP1, which infects Bacillus subtilis[19] (Fig. 1)
Summary
Host cell initially depends on the reversible binding to WTAs, which accelerates the subsequent irreversible binding to membrane receptor YueB8. It is very well known that phages or mainly siphoviruses play vital roles in the virulence, adaptation, and evolution of S. aureus[1,2]. We have shown that staphylococcal siphoviruses use α-O-GlcNAc modified WTA as a receptor[11] and that WTA structures govern phage-mediated horizontal transfer of SaPIs among major bacterial pathogens[12]. We report the identification and characterization of the φ11 RBP and the major components of its receptor in the cell wall of S. aureus. These data provide novel insight into phage-host recognition at the staphylococcal cell surface, and establish a molecular basis to develop novel diagnostics and therapeutic treatments of S. aureus infection
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