An optimized synthetic-bioinformatic natural product antibiotic sterilizes multidrug-resistant Acinetobacter baumannii-infected wounds

Xavier Vila-Farres, John Chu, Melinda A. Ternei, Christophe Lemetre, Steven Park, David S. Perlin, Sean F. Brady

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The antibiotic paenimucillin A was originally identified using a cultureindependent 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.

Original languageEnglish (US)
Article numbere00528-17
JournalmSphere
Volume3
Issue number1
DOIs
StatePublished - Jan 1 2018

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Microbiology

Keywords

  • Acinetobacter baumannii
  • Antibiotics
  • Syn-BNP
  • Wound infections

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