Diversity in bacterial lysis systems: bacteriophages show the way

Abstract

Bacteriophages have developed multiple host cell lysis strategies to promote release of descendant virions from infected bacteria. This review is focused on the lysis mechanisms employed by tailed double-stranded DNA bacteriophages, where new developments have recently emerged. These phages seem to use a least common denominator to induce lysis, the so-called holin-endolysin dyad. Endolysins are cell wall-degrading enzymes whereas holins form 'holes' in the cytoplasmic membrane at a precise scheduled time. The latter function was long viewed as essential to provide a pathway for endolysin escape to the cell wall. However, recent studies have shown that phages can also exploit the host cell secretion machinery to deliver endolysins to their target and subvert the bacterial autolytic arsenal to effectively accomplish lysis. In these systems the membrane-depolarizing holin function still seems to be essential to activate secreted endolysins. New lysis players have also been uncovered that promote degradation of particular bacterial cell envelopes, such as that of mycobacteria.

Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications

“…Multiple cell lysis strategies that promote release of the virions from phage-infected bacteria have been described elsewhere (4). In general, the lysis genes are found in cassettes localized together on the phage chromosome, and these include at least two genes, one that encodes a small protein which spans the cytoplasmic membrane from one to four times as transmembrane ␣-helical sequences (TMSs) ( Fig.…”

“…Endolysins are genome-or phage-encoded enzymes that can be of at least five different types (4,7). Many of them are made without targeting signal sequences, sequences that are characteristic of proteins exported via the general secretory pathway, the Sec translocase (8) (see the Transporter Classification Database [TCDB]; www.tcdb.org; TC no.…”

“…Holins allow the endolysins to gain access to the cell wall, where they exert their actions by cleaving various bonds in the peptidoglycan polymer, depending on the type of endolysin (4,13). Genes encoding holin proteins and their target peptidoglycan hydrolases have been identified in a wide variety of Gram-negative and Gram-positive bacteria and their phages (1,(14)(15)(16)(17).…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Phage-Related Therapy

“…These lysis-deficient phages successfully induced MRSA death in mice infection model without lysis induced side effects such as septic shock or toxic shock syndrome, possibly based on the sole activity of holin [48,49].…”

Molecular Dissection of Phage Endolysin

“…2 To whom correspondence should be addressed: Microbiology membrane rich in mycolic acid. Holin, in several bacteriophages, is required for the transfer of lysins from the cytosol (its site of production) to the periplasm (its site of action) (23,24). However, whether it has similar function in D29 or other mycobacteriophages remains to be elucidated.…”