| Autor: |
Chamakura KR; Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M AgriLife Research, Texas A&M University, College Station, TX, 77843-2128, USA., Sham LT; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02215, USA., Davis RM; Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA., Min L; Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M AgriLife Research, Texas A&M University, College Station, TX, 77843-2128, USA., Cho H; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02215, USA., Ruiz N; Department of Microbiology, Ohio State University, Columbus, OH, 43210, USA., Bernhardt TG; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02215, USA. thomas@hms.harvard.edu., Young R; 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. |
| Abstrakt: |
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 A 2 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, Lys M , of the Escherichia coli levivirus M 5 . We show that Lys M 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 Lys M inhibits a distinct step in the PG synthesis pathway from the A 2 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. |
Full text from SpringerLink