Cell wall hydrolases and antibiotics: exploiting synergy to create efficacious new antimicrobial treatments.
Cell wall hydrolases (CWH) are enzymes that build, remodel and degrade peptidoglycan within bacterial cell walls and serve essential roles in cell-wall metabolism, bacteriophage adsorption and bacteriolysis, environmental niche expansion, as well as eukaryotic innate immune defense against bacterial infection. Some CWHs, when tested as recombinant purified proteins, have been shown to have bactericidal activities both as single agents and in combinations with other antimicrobials, displaying synergies in vitro and potent activities in animal models of infection greater than the single agents alone. We summarize in vitro, in vivo, and mechanistic studies that illustrate ACWH synergy with antibiotics, antimicrobial peptides, and other ACWHs, underscoring the overall synergistic potential of the ACWH class.
ContraFect Corporation, 28 Wells Avenue, 3rd Floor, Yonkers, NY 10701, United States. Electronic address: mwittekind@contrafect.com.
Michael
M
Wittekind
ContraFect Corporation, 28 Wells Avenue, 3rd Floor, Yonkers, NY 10701, United States.
Raymond
R
Schuch
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins / Q000494:pharmacology*; D001433:Bacteriolysis / Q000187:drug effects*; D002473:Cell Wall / Q000378:metabolism*; D004195:Disease Models, Animal; D004357:Drug Synergism; D008248:Lysostaphin / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology; D010457:Peptidoglycan / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010456:Peptides, Cyclic; D010457:Peptidoglycan; C086618:ranalexin; D014640:Vancomycin; D008248:Lysostaphin; D011112:Polymyxin B