Phage single-gene lysis: Finding the weak spot in the bacterial cell wall

J Biol Chem. 2019 Mar 8;294(10):3350-3358. doi: 10.1074/jbc.TM118.001773. Epub 2018 Nov 12.

Abstract

In general, the last step in the vegetative cycle of bacterial viruses, or bacteriophages, is lysis of the host. dsDNA phages require multiple lysis proteins, including at least one enzyme that degrades the cell wall (peptidoglycan (PG)). In contrast, the lytic ssDNA and ssRNA phages have a single lysis protein that achieves cell lysis without enzymatically degrading the PG. Here, we review four "single-gene lysis" or Sgl proteins. Three of the Sgls block bacterial cell wall synthesis by binding to and inhibiting several enzymes in the PG precursor pathway. The target of the fourth Sgl, L from bacteriophage MS2, is still unknown, but we review evidence indicating that it is likely a protein involved in maintaining cell wall integrity. Although only a few phage genomes are available to date, the ssRNA Leviviridae are a rich source of novel Sgls, which may facilitate further unraveling of bacterial cell wall biosynthesis and discovery of new antibacterial agents.

Keywords: MraY; MurA; MurJ; antibiotic; autolysin; bacteriophage; cell wall; chaperone DnaJ (DnaJ); enzyme inhibitor; flippase; peptidoglycan; peptidoglycan biosynthesis; phage; single-gene lysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacteria* / genetics
  • Bacteria* / metabolism
  • Bacteria* / virology
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Cell Wall* / genetics
  • Cell Wall* / metabolism
  • Cell Wall* / virology
  • Genes, Viral / physiology*
  • Levivirus / physiology*
  • Peptidoglycan* / genetics
  • Peptidoglycan* / metabolism

Substances

  • Bacterial Proteins
  • Peptidoglycan

Associated data

  • PDB/4J72
  • PDB/5T77