Analysis of the pseudomonas aeruginosa aminoglycoside differential resistomes allows defining genes simultaneously involved in intrinsic antibiotic resistance and virulence

Fernando Sanz-García, Carolina Alvarez-Ortega, JORGE ANDRES OLIVARES PACHECO, Paula Blanco, José Luis Martínez, Sara Hernando-Amado

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

High-throughput screening of transposon insertion libraries is a useful strategy for unveiling bacterial genes whose inactivation results in an altered susceptibility to antibiotics. A potential drawback of these studies is they are usually based on just one model antibiotic for each structural family, under the assumption that the results can be extrapolated to all members of said family. To determine if this simplification is appropriate, we have analyzed the susceptibility of mutants of Pseudomonas aeruginosa to four aminoglycosides. Our results indicate that each mutation produces different effects on susceptibility to the tested aminoglycosides, with only two mutants showing similar changes in the susceptibility to all studied aminoglycosides. This indicates that the role of a particular gene in the resistome of a given antibiotic should not be generalized to other members of the same structural family. Five aminoglycoside-hypersusceptible mutants inactivating glnD, hflK, PA2798, PA3016, and hpf were chosen for further analysis in order to elucidate if lower aminoglycoside susceptibility correlates with cross-hypersusceptibility to other antibiotics and with impaired virulence. Our results indicate that glnD inactivation leads to increased cross-susceptibility to different antibiotics. The mutant in this gene is strongly impaired in virulence traits such as pyocyanin production, biofilm formation, elastase activity, and swarming motility and the ability to kill Caenorhabditis elegans. Thus, GlnD might be an interesting target for developing antibiotic coadjuvants with antiresistance and antivirulence properties against P. aeruginosa.

Original languageEnglish
Article numbere00185-19
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number5
DOIs
StatePublished - 1 May 2019

Keywords

  • Adjuvants
  • Intrinsic resistome
  • Pseudomonas aeruginosa
  • Virulence

Fingerprint Dive into the research topics of 'Analysis of the pseudomonas aeruginosa aminoglycoside differential resistomes allows defining genes simultaneously involved in intrinsic antibiotic resistance and virulence'. Together they form a unique fingerprint.

Cite this