Mutations in Ribosomal Protein RplA or Treatment with Ribosomal Acting Antibiotics Activates Production of Aminoglycoside Efflux Pump SmeYZ in Stenotrophomonas maltophilia

Antimicrob Agents Chemother. 2020 Jan 27;64(2):e01524-19. doi: 10.1128/AAC.01524-19. Print 2020 Jan 27.

Abstract

Aminoglycoside resistance in Stenotrophomonas maltophilia is multifactorial, but the most significant mechanism is overproduction of the SmeYZ efflux system. By studying laboratory-selected mutants and clinical isolates, we show here that damage to the 50S ribosomal protein L1 (RplA) activates SmeYZ production. We also show that gentamicin and minocycline, which target the ribosome, induce expression of smeYZ These findings explain the role of SmeYZ in both intrinsic and mutationally acquired aminoglycoside resistance.

Keywords: efflux; gentamicin; ribosomal mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / metabolism*
  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Bacterial / genetics
  • Gentamicins / pharmacology
  • Microbial Sensitivity Tests
  • Minocycline / pharmacology
  • Mutation
  • Ribosomal Proteins / genetics*
  • Ribosomes / drug effects*
  • Stenotrophomonas maltophilia / drug effects
  • Stenotrophomonas maltophilia / genetics*
  • Stenotrophomonas maltophilia / metabolism

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Gentamicins
  • Ribosomal Proteins
  • ribosomal protein L1
  • Minocycline