An Optimized Synthetic-Bioinformatic Natural Product Antibiotic Sterilizes Multidrug-Resistant Acinetobacter baumannii-Infected Wounds.

ABSTRACT: The antibiotic paenimucillin A was originally identified using a culture-independent synthetic-bioinformatic natural product (syn-BNP) discovery approach. Here we report on a bioinformatics-guided survey of paenimucillin A analogs that led to the discovery of paenimucillin C. Paenimucillin C inhibits the growth of multidrug-resistant (MDR) Acinetobacter baumannii clinical isolates, as well as other Gram-negative bacterial pathogens. In a rat cutaneous wound model, it completely sterilized MDR A. baumannii wound infections with no sign of rebound. Mechanistic studies point to a membrane-associated mode of action that results in leakage of intracellular contents. IMPORTANCE Natural product-inspired antibiotics have saved millions of lives and played a critical role in modern medicine. Howeve

SUBMITTER: Vila-Farres X 

PROVIDER: S-EPMC5784245 | biostudies-literature | 2018 Jan-Feb

REPOSITORIES: biostudies-literature