Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials

Nat Microbiol. 2021 Feb;6(2):157-161. doi: 10.1038/s41564-020-00830-7. Epub 2021 Jan 11.

Abstract

We characterized two bacteriophages, ΦFG02 and ΦCO01, against clinical isolates of Acinetobacter baumannii and established that the bacterial capsule is the receptor for these phages. Phage-resistant mutants harboured loss-of-function mutations in genes responsible for capsule biosynthesis, resulting in capsule loss and disruption of phage adsorption. The phage-resistant strains were resensitized to human complement, beta-lactam antibiotics and alternative phages and exhibited diminished fitness in vivo. Using a mouse model of A. baumannii infection, we showed that phage therapy was effective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / microbiology*
  • Acinetobacter Infections / therapy*
  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / virology*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Capsules / virology
  • Bacteriophages / physiology*
  • Complement System Proteins / pharmacology
  • Disease Models, Animal
  • Drug Resistance, Bacterial
  • Female
  • Humans
  • Loss of Function Mutation
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Phage Therapy*
  • beta-Lactamase Inhibitors / pharmacology

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors
  • Complement System Proteins