Bacteriophage and Peptidoglycan Degrading Enzymes with Antimicrobial Applications

Abstract

Peptidoglycan is the major structural component of bacterial cell walls. In this era of increasingly antibiotic resistant pathogens, peptidoglycan hydrolases that degrade this important cell wall structure have emerged as a potential novel source of new antimicrobials. Included in this class are bacteriocins (lysostaphin), lysozyme, and bacteriophage endolysins. Bacteriophage are viruses that infect and utilize bacteria as their host. They can reside in the bacterial genome as a prophage, or enter the lytic phase, take over the bacterial gene expression machinery, synthesize new phage particles, lyse the host, and release up to hundreds of phage progeny. Lysis occurs during the late phase of the lytic cycle when the phage endolysin and a holin molecule are produced. The holin creates holes in the cells lipid bilayer allowing the phage endolysin (peptidoglycan hydrolase) to escape and degrade the structural portion of the cell wall. These (and other phage encoded proteins) have been shown to inhibit bacterial growth. The ability to inhibit growth or kill bacteria make both the bacteriophage and their gene products a rich source of potential antimicrobials. This review summarizes the recent resurgence of these potential antimicrobials as both diagnostic and therapeutic agents and identifies recent patents that describe these technologies.

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

“…1.E.10.1.3) and an endolysin from the phage SMP to lyse S. suis and other pathogens, including S. aureus. Their surprising results led these authors to the conclusion that a holin, used in conjunction with a lysin, can function as an antibacterial agent to help solve the drug resistance problem arising in these and other Grampositive bacterial pathogens (14,80).…”

“…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). While possible homologues are present in archaea (see holin families 1.E.3, 1.E.14, and 1.E.43 in TCDB), the functions of these proteins are not yet defined.…”

Identification and characterization of HolGH15: the holin of Staphylococcus aureus bacteriophage GH15

“…Holins have been identified in a wide variety of bacteriophages (Catalão et al, 2010;Donovan, 2007;Wang et al, 2000). To date, 52 families of holins have been identified, and representative well-characterized members, as well as distant homologues with unknown functions, have been entered into the Transporter Classification Database (Reddy & Saier, 2013).…”

Characterization of a Novel LysM Domain from Lactobacillus fermentum Bacteriophage Endolysin and Its Use as an Anchor To Display Heterologous Proteins on the Surfaces of Lactic Acid Bacteria

“…Endolysins from bacteriophages are cell wall hydrolases involved in cell lysis to release the progeny particles from the host cells (9,30). Most endolysins lack a signal peptide and are translocated across the membrane by the aid of the holin protein.…”