AUTHOR=Schuch Raymond , Cassino Cara , Vila-Farres Xavier 

TITLE=Direct Lytic Agents: Novel, Rapidly Acting Potential Antimicrobial Treatment Modalities for Systemic Use in the Era of Rising Antibiotic Resistance

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.841905

DOI=10.3389/fmicb.2022.841905

ISSN=1664-302X

ABSTRACT=Direct lytic agents (DLAs) are novel antimicrobial compounds with unique mechanisms of action based on rapid cell wall destabilization and bacteriolysis.  DLAs include two classes of purified polypeptides - lysins (peptidoglycan hydrolase enzymes) and amurins (outer membrane targeting peptides).  Their intended use is to kill bacteria in a manner that is complimentary to and synergistic with traditional antibiotics without selection for DLA resistance.  Lysins were originally described as having activity against Gram-positive pathogens and of those, exebacase, is the first to have advanced into Phase 3 of clinical development.  Recently, both engineered and native DLAs have now been described with potent bactericidal activity against a range of Gram-negative pathogens, including multi drug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii.  Importantly, novel DLAs targeting Gram-negatives, including the lysin CF-370 and the amurin peptides, are active in biological matrices (blood/serum) and, as such, offer promise for therapeutic use as systemically administered agents for the treatment of life-threatening invasive infections.  In this review, DLAs are discussed as potential new classes of antimicrobial biologics that can be used to treat serious systemic infections.