A Kayvirus Distant Homolog of Staphylococcal Virulence Determinants and VISA Biomarker Is a Phage Lytic Enzyme

Abstract

Staphylococcal bacteriophages of the <i>Kayvirus</i> genus are candidates for therapeutic applications. One of their proteins, Tgl, is slightly similar to two staphylococcal virulence factors, secreted autolysins of lytic transglycosylase motifs IsaA and SceD. We show that Tgl is a lytic enzyme secreted by the bacterial transport system and localizes to cell peripheries like IsaA and SceD. It causes lysis of <i>E. coli</i> cells expressing the cloned <i>tgl</i> gene, but could be overproduced when depleted of signal peptide. <i>S. aureus</i> cells producing Tgl lysed in the presence of nisin, which mimics the action of phage holin. In vitro, Tgl protein was able to destroy <i>S. aureus</i> cell walls. The production of Tgl decreased <i>S. aureus</i> tolerance to vancomycin, unlike the production of SceD, which is associated with decreased sensitivity to vancomycin. In the genomes of kayviruses, the <i>tgl</i> gene is located a few genes away from the <i>lysK</i> gene, encoding the major endolysin. While <i>lysK</i> is a late phage gene, <i>tgl</i> can be transcribed by a host RNA polymerase, like phage early genes. Taken together, our data indicate that <i>tgl</i> belongs to the kayvirus lytic module and encodes an additional endolysin that can act in concert with LysK in cell lysis.