Wall teichoic acid substitution with glucose governs phage susceptibility ofStaphylococcus epidermidis

Abstract

AbstractThe species- and clone-specific susceptibility ofStaphylococcuscells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycocodes of phage-WTA interaction in the opportunistic pathogenStaphylococcus epidermidisand in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a newS. epidermidisWTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses.S. epidermidisglycerolphosphate WTA was found to be modified with glucose in atagE-dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. ΦE72 transduced several other CoNS species encoding TagE homologs suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits inter-species horizontal gene transfer. Our study unravels a crucial mechanism of phage-Staphylococcusinteraction and of horizontal gene transfer and it will help in the design of anti-staphylococcal phage therapies.ImportancePhages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genusStaphylococcusbind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogenStaphylococcus epidermidisand in other coagulase-negativeStaphylococcus(CoNS) species has remained unknown. We describe thatS. epidermidisglycosylates its WTA backbone with glucose and we identify a cluster of three genes, responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus ΦE72 suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.