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Nat Microbiol. 2017 Nov;2(11):1480-1484. doi: 10.1038/s41564-017-0023-4. Epub 2017 Sep 11.

A viral protein antibiotic inhibits lipid II flippase activity.

Author information

1
Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M AgriLife Research, Texas A&M University, College Station, TX, 77843-2128, USA.
2
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02215, USA.
3
Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA.
4
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02215, USA. thomas@hms.harvard.edu.
5
Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M AgriLife Research, Texas A&M University, College Station, TX, 77843-2128, USA. ryland@tamu.edu.

Abstract

For bacteriophage infections, the cell walls of bacteria, consisting of a single highly polymeric molecule of peptidoglycan (PG), pose a major problem for the release of progeny virions. Phage lysis proteins that overcome this barrier can point the way to new antibacterial strategies 1 , especially small lytic single-stranded DNA (the microviruses) and RNA phages (the leviviruses) that effect host lysis using a single non-enzymatic protein 2 . Previously, the A2 protein of levivirus Qβ and the E protein of the microvirus ϕX174 were shown to be 'protein antibiotics' that inhibit the MurA and MraY steps of the PG synthesis pathway 2-4 . Here, we investigated the mechanism of action of an unrelated lysis protein, LysM, of the Escherichia coli levivirus M 5 . We show that LysM inhibits the translocation of the final lipid-linked PG precursor called lipid II across the cytoplasmic membrane by interfering with the activity of MurJ. The finding that LysM inhibits a distinct step in the PG synthesis pathway from the A2 and E proteins indicates that small phages, particularly the single-stranded RNA (ssRNA) leviviruses, have a previously unappreciated capacity for evolving novel inhibitors of PG biogenesis despite their limited coding potential.

PMID:
28894177
PMCID:
PMC5764540
DOI:
10.1038/s41564-017-0023-4
[Indexed for MEDLINE]
Free PMC Article

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