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Multidrug Adaptive Resistance of Pseudomonas aeruginosa Swarming Cells

Shannon R Coleman1, Travis Blimkie1, Reza Falsafi1

  • 1Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.

Antimicrobial Agents and Chemotherapy
|December 18, 2019
PubMed

Insights

Swarming motility in Pseudomonas aeruginosa enhances resistance to many antibiotics, but not polymyxin B. This multideterminant resistance involves numerous gene dysregulations, including specific mutations conferring tobramycin and trimethoprim resistance.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Antimicrobial Resistance

Background:

  • Swarming surface motility in *Pseudomonas aeruginosa* is linked to increased virulence and antibiotic resistance.
  • Previous studies indicated swarming enhances resistance, but mechanisms remain incompletely understood.

Purpose of the Study:

  • To investigate the transcriptomic changes associated with swarming in *P. aeruginosa* PA14.
  • To identify genes and pathways contributing to swarming-mediated antibiotic resistance.

Main Methods:

  • Transcriptomic analysis (RNA-Seq) of swarming versus swimming *P. aeruginosa* PA14 cells.
  • Gene expression analysis of swarming cells treated with tobramycin.
  • Mutant analysis of dysregulated genes for antibiotic resistance phenotypes during swarming.
  • Reverse transcriptase quantitative PCR (qRT-PCR) for gene expression validation.

Main Results:

  • Swarming cells exhibited increased resistance to multiple antibiotics (aminoglycosides, β-lactams, etc.) but not polymyxin B.
  • RNA-Seq revealed 1,581 dysregulated genes in swarming cells, including regulators, virulence factors, and ribosomal genes.
  • 41 mutants in dysregulated genes showed enhanced tobramycin resistance during swarming, confirming multideterminant resistance.
  • Mutants in *prtN* and *wbpW* displayed increased tobramycin resistance, with *prtN* also showing trimethoprim resistance.
  • Tobramycin treatment upregulated the MexXY efflux pump and downregulated virulence factors in swarming cells.

Conclusions:

  • Swarming motility significantly enhances *P. aeruginosa*'s resistance to a broad spectrum of antibiotics through complex genetic regulation.
  • Specific gene dysregulations, including downregulation of *prtN* and *wbpW*, contribute to antibiotic resistance during swarming.
  • The MexXY efflux pump plays a role in tobramycin resistance under swarming conditions.
Keywords:
Pseudomonas aeruginosaRNA-Seqantibiotic resistanceswarming motilitytobramycin

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