title: An accessory wall teichoic acid glycosyltransferase protects Staphylococcus aureus from the lytic activity of Podoviridae.
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.
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Li
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Gerlach
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.
authors.forename: Xin
authors.initials: X
authors.lastname: Du
authors.affiliation: Microbiology and Infection Control, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Larsen
authors.affiliation: Microbiology and Infection Control, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.|Pathogen Genomics Division, Translational Genomics Research Institute, 3051 W Shamrell Blvd, Flagstaff, 86001 Arizona, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Stegger
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kühner
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.|Institute of Inflammation &Repair, The University of Manchester, Manchester, United Kingdom.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Xia
authors.affiliation: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.|German Center for Infection Research (DZIF), partner site Tübingen, 72076 Tübingen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Winstel
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000502:physiology*; D019143:Evolution, Molecular; D016695:Glycosyltransferases / Q000502:physiology*; D054884:Host-Pathogen Interactions; D008969:Molecular Sequence Data; D010802:Phylogeny; D017902:Podoviridae / Q000502:physiology*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000821:virology
chemical_list: D001426:Bacterial Proteins; D016695:Glycosyltransferases