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Overexpression of MexCD-OprJ reduces Pseudomonas aeruginosa virulence by increasing its susceptibility to

Inmaculada Martínez-Ramos1, Xavier Mulet, Bartolomé Moyá

  • 1Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares, Palma de Mallorca, Spain.

Antimicrobial Agents and Chemotherapy
|January 15, 2014
PubMed

Insights

Pseudomonas aeruginosa strains with antibiotic resistance showed altered interactions with the host immune system. Specifically, nfxB mutants were more susceptible to complement, impacting their ability to infect mice.

Area of Science:

  • Microbiology
  • Immunology
  • Bacterial Pathogenesis

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic and acquired antimicrobial resistance.
  • The complement system is a crucial part of the innate immune system that P. aeruginosa must evade to cause infection.

Purpose of the Study:

  • To investigate how different antimicrobial resistance phenotypes in P. aeruginosa affect its susceptibility to complement-mediated killing.
  • To elucidate the mechanisms underlying changes in complement resistance in antibiotic-resistant strains.

Main Methods:

  • Evaluation of complement-mediated killing resistance in isogenic P. aeruginosa strains with various antimicrobial resistance profiles.
  • Analysis of the role of the MexCD-OprJ efflux pump in complement resistance.
  • Assessment of C3 opsonization levels.
  • In vivo mouse lung infection model to evaluate infectivity.

Main Results:

  • The nfxB mutant exhibited significantly increased susceptibility to complement-mediated killing compared to the wild-type strain.
  • This heightened susceptibility was linked to the overexpression of the MexCD-OprJ efflux pump.
  • Overexpression of MexCD-OprJ resulted in increased C3 opsonization and a diminished capacity for P. aeruginosa to infect mouse lungs.

Conclusions:

  • Acquisition of antibiotic resistance in P. aeruginosa can alter its interaction with the host immune system, specifically affecting complement resistance.
  • The MexCD-OprJ efflux pump plays a role in modulating P. aeruginosa's susceptibility to complement.
  • Antibiotic resistance mechanisms may have unintended consequences on bacterial virulence and host immune evasion.

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