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

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.

Structural basis for the adsorption of a single-stranded RNA bacteriophage

“…Then the Mat, along with the genomic RNA (gRNA), is released from the viral capsid and taken up by the host, presumably through the retractile force of the host pilus 6 . Cytosolic internalization of the gRNA initiates the expression of the viral genes, resulting in replication, virion morphogenesis, and lysis of the host 7 .…”

Rapid de novo evolution of lysis genes in single-stranded RNA phages

“…This led to the identification of 35 unique Sgls (33 in the initial screen plus two evolved Sgls) exhibiting activity in E. coli, each potentially representing a distinct mechanism to effect host cell lysis. Moreover, a BLAST search with the expanded pool of Sgls against the recently deposited tens of thousands of leviviruses returned only a handful of hits, which suggests that Sgls are extremely diverse and remain vastly untapped as a source for peptides that attack essential cellular functions; i.e., for protein antibiotics 24,25 . One lysis gene per phage genome has been the paradigm for small lytic phages (microviruses and leviviruses) since the late 1970s, when the first genomes, φX174 and MS2, respectively, were sequenced 26,27 .…”

Reverse Genetic Systems for Pseudomonas aeruginosa Leviphages

“…Besides, it is also important to select appropriate vectors, given that the proteins of RNA phages might be toxic to bacterial cells. For example, LP directly inhibits the enzymes of the peptidoglycan synthesis pathway [11]: RP can sequester some proteins required for the ribosome function [12]. To this end, we have to consider both the copy number and the genetic context for the basal/leaky expression of the cloned gene fragments.…”