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.