Mutations in the β-Subunit of the RNA Polymerase Impair the Surface-Associated Motility and Virulence of Acinetobacter baumannii

Infect Immun. 2017 Jul 19;85(8):e00327-17. doi: 10.1128/IAI.00327-17. Print 2017 Aug.

Abstract

Acinetobacter baumannii is a major cause of antibiotic-resistant nosocomial infections worldwide. In this study, several rifampin-resistant spontaneous mutants obtained from the A. baumannii ATCC 17978 strain that differed in their point mutations in the rpoB gene, encoding the β-subunit of the RNA polymerase, were isolated. All the mutants harboring amino acid substitutions in position 522 or 540 of the RpoB protein were impaired in surface-associated motility and had attenuated virulence in the fertility model of Caenorhabditis elegans The transcriptional profile of these mutants included six downregulated genes encoding proteins homologous to transporters and metabolic enzymes widespread among A. baumannii clinical isolates. The construction of knockout mutants in each of the six downregulated genes revealed a significant reduction in the surface-associated motility and virulence of four of them in the A. baumannii ATCC 17978 strain, as well as in the virulent clinical isolate MAR002. Taken together, our results provide strong evidence of the connection between motility and virulence in this multiresistant nosocomial pathogen.

Keywords: Acinetobacter baumannii; rifampin resistance; rpoB; surface-associated motility.

MeSH terms

  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii / enzymology
  • Acinetobacter baumannii / genetics*
  • Acinetobacter baumannii / pathogenicity*
  • Acinetobacter baumannii / physiology
  • Amino Acid Substitution
  • Animals
  • Bacterial Proteins / genetics
  • Caenorhabditis elegans / microbiology
  • Cross Infection / microbiology
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism*
  • Down-Regulation
  • Drug Resistance, Multiple, Bacterial
  • Gene Expression Profiling
  • Gene Knockout Techniques
  • Humans
  • Membrane Transport Proteins / genetics
  • Point Mutation*
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • Membrane Transport Proteins
  • DNA-Directed RNA Polymerases