Bacteriophage and peptidoglycan degrading enzymes with antimicrobial applications.
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.
Donovan
David M
DM
Biotechnology and Germplasm Laboratory, ANRI, ARS, USDA, Bldg. 230, Room 104, BARC-East, 10300 Baltimore Ave, Beltsville, MD 20705-2350, USA. ddonovan@anri.barc.usda.gov
D000890:Anti-Infective Agents / Q000737:chemistry / Q000627:therapeutic use*; D001419:Bacteria / Q000378:metabolism / Q000821:virology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D001435:Bacteriophages / Q000201:enzymology*; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D010330:Patents as Topic; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D010457:Peptidoglycan; D014764:Viral Proteins; D009113:Muramidase; D010450:Endopeptidases; C001143:endolysin