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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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PmrA Mutations in Drug-Resistant Acinetobacter baumannii Affect Sensor Kinase-Response Regulator Interaction and

Felicia E Jaimes1, Alexander D Hondros1, Jude Kinkead1

  • 1Department of Biochemistry & Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 27858, USA.

Microorganisms
|November 27, 2025
PubMed

Insights

Mutations in the PmrA protein of Acinetobacter baumannii reduce its ability to receive a key activating signal, leading to increased resistance against polymyxin antibiotics. This impacts last-resort drug effectiveness.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Multidrug resistance in Acinetobacter baumannii is a critical public health concern.
  • Polymyxins are last-line antibiotics, but resistance is emerging in A. baumannii.
  • Polymyxin resistance is linked to the PmrAB two-component system, involving PmrA-mediated lipooligosaccharide modification.

Purpose of the Study:

  • To investigate the functional impact of specific PmrA mutations found in resistant A. baumannii isolates.
  • To understand how these mutations affect PmrA's interaction with PmrB and its phosphorylation status.

Main Methods:

  • Characterization of five PmrA mutations (D10N, M12I, I13M, G54E, S119T).
  • Assessed changes in PmrA DNA-binding affinity, dimerization, phosphorylation, and structure.
  • Evaluated the impact on PmrA's interaction with the sensor kinase PmrB.

Main Results:

  • The studied PmrA mutations impair the protein's ability to accept a phosphoryl group from PmrB.
  • This impaired phosphorylation may result from disrupted PmrB-PmrA interaction or perturbation of PmrA's active site.
  • Slowed phosphorylation can potentially enhance PmrA-mediated gene transcription.

Conclusions:

  • PmrA mutations conferring polymyxin resistance in A. baumannii affect its phosphorylation mechanism.
  • Understanding these molecular mechanisms is crucial for combating antibiotic resistance.
  • These findings provide insights into PmrA-regulated resistance pathways in Acinetobacter baumannii.
Keywords:
antibiotic resistancepoint-mutantsregulatory networksresponse regulatorstranscriptional controltwo-component systems

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