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Nitrate Respiration Promotes Polymyxin B Resistance in Pseudomonas aeruginosa

Bi-O Kim1, Hye-Jeong Jang1, In-Young Chung1

  • 1Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Gyeonggi-do, Korea.

Antioxidants & Redox Signaling
|May 7, 2020
PubMed

Insights

Nitrate respiration (NR) in Pseudomonas aeruginosa contributes to resistance against Polymyxin B (PMB), an antibiotic requiring reactive oxygen species (ROS) for its activity. This NR-mediated resistance is common in clinical isolates and offers a potential therapeutic target.

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Biochemistry

Background:

  • Polymyxin B (PMB) efficacy relies on reactive oxygen species (ROS), but mechanisms of PMB resistance in Pseudomonas aeruginosa are unclear.
  • Nitrate respiration (NR) is investigated as a potential factor influencing PMB resistance in P. aeruginosa.

Purpose of the Study:

  • To elucidate the role of nitrate respiration (NR) in mediating Polymyxin B (PMB) resistance in Pseudomonas aeruginosa.
  • To determine if NR impacts ROS generation or degradation in the context of PMB resistance.

Main Methods:

  • Comparative analysis of PMB minimum inhibitory concentrations (MICs) in P. aeruginosa strains with varying NR levels.
  • Transcriptomic and phenotypic analyses of wild-type strains and their NR mutants.
  • Assessment of PMB efficacy in Drosophila infection models.

Main Results:

  • Higher NR levels in P. aeruginosa PAO1 correlated with increased PMB resistance (higher MIC) compared to PA14.
  • NR-mediated PMB resistance was observed to be independent of the major catalase (KatA).
  • NR was found to be a common trait among clinical P. aeruginosa isolates, linked to higher PMB resistance.

Conclusions:

  • Nitrate respiration (NR) is a significant contributor to intrinsic Polymyxin B (PMB) resistance in Pseudomonas aeruginosa.
  • NR may influence ROS generation, impacting PMB's bactericidal activity.
  • Targeting NR could be a strategy to overcome PMB resistance in P. aeruginosa infections.
Keywords:
Pseudomonas aeruginosaantibiotic resistancenitrate respirationpolymyxin Breactive oxygen species

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