The novel MFS efflux pump SxtP, regulated by the LysR-type transcriptional activator SxtR, is involved in the susceptibility to sulfamethoxazole/trimethoprim (SXT) and the pathogenesis of Acinetobacter baumannii

Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0071224. doi: 10.1128/aac.00712-24. Epub 2024 Aug 28.

Abstract

Acinetobacter baumannii is a notorious opportunistic pathogen responsible for healthcare-associated infections worldwide. Efflux pumps play crucial roles in mediating antimicrobial resistance, motility, and virulence. In this study, we present the identification and characterization of the new A. baumannii efflux pump SxtP belonging to the MFS superfamily (major facilitator superfamily), along with its associated activator LysR-type transcriptional regulator (LTTR) SxtR, demonstrating their roles in sulfamethoxazole/trimethoprim (also known as co-trimoxazole or SXT) resistance, surface-associated motility and virulence.

Keywords: Acinetobacter; LysR-type transcriptional regulator; MFS efflux pump; co-trimoxazole.

MeSH terms

  • Acinetobacter Infections / drug therapy
  • Acinetobacter Infections / microbiology
  • Acinetobacter baumannii* / drug effects
  • Acinetobacter baumannii* / genetics
  • Acinetobacter baumannii* / metabolism
  • Acinetobacter baumannii* / pathogenicity
  • Animals
  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Drug Resistance, Multiple, Bacterial / genetics
  • Gene Expression Regulation, Bacterial
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mice
  • Microbial Sensitivity Tests*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Trimethoprim, Sulfamethoxazole Drug Combination* / pharmacology
  • Virulence / genetics

Substances

  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Transport Proteins
  • Transcription Factors