Abstract
Staphylococcal bacteriophages of the Kayvirus 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 E. coli cells expressing the cloned tgl gene, but could be overproduced when depleted of signal peptide. S. aureus cells producing Tgl lysed in the presence of nisin, which mimics the action of phage holin. In vitro, Tgl protein was able to destroy S. aureus cell walls. The production of Tgl decreased S. aureus tolerance to vancomycin, unlike the production of SceD, which is associated with decreased sensitivity to vancomycin. In the genomes of kayviruses, the tgl gene is located a few genes away from the lysK gene, encoding the major endolysin. While lysK is a late phage gene, tgl can be transcribed by a host RNA polymerase, like phage early genes. Taken together, our data indicate that tgl belongs to the kayvirus lytic module and encodes an additional endolysin that can act in concert with LysK in cell lysis.
Highlights
Staphylococcus aureus is one of the most challenging bacterial pathogens because of the increasing number and spread of antibiotic-resistant strains that are a serious threat to health and life [1]
Analysis of the 230-aa Tgl protein sequence reveals that it contains a core lysozyme-like domain motif at its C-terminal end with a conserved glutamate, which is involved in the catalytic activity of core lysozyme-like domain-containing proteins, including E. coli soluble lytic transglycosylase Slt (Figure 1) [68]
Staphylococcal phages of certain Twortvirinae genera, kayviruses among them, encode a distant homolog (Tgl) of two secreted autolysins and virulence factors of S. aureus (IsaA and SceD), which they apparently acquired after the differentiation of Twortvirinae
Summary
Staphylococcus aureus is one of the most challenging bacterial pathogens because of the increasing number and spread of antibiotic-resistant strains that are a serious threat to health and life [1]. Bacteriophage therapy may become a future option of choice to fight infections with antibiotic-resistant. Phages target bacteria of certain strains or species independently of bacterial resistance to antibiotics. Bacteriophages are harmless to eukaryotic cells and propagate in a self-limiting manner, which is controlled by the availability of a sensitive host [3]. Bacteriophages specific for certain bacterial pathogens do not destroy natural human or animal microflora and do not cause the selection of antibiotic-resistant strains [4].
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