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A PmrB-Regulated Deacetylase Required for Lipid A Modification and Polymyxin Resistance in Acinetobacter baumannii

Chui-Yoke Chin1, Kelsey A Gregg2, Brooke A Napier3

  • 1Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, USA Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

Antimicrobial Agents and Chemotherapy
|October 14, 2015
PubMed

Insights

Emerging polymyxin antibiotic resistance in Gram-negative bacteria is a major threat. Researchers found Acinetobacter baumannii NaxD deacetylase drives resistance by modifying lipid A, offering a potential new drug target.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Discovery

Background:

  • Polymyxin antibiotics are crucial last-resort treatments against Gram-negative bacterial infections.
  • Rising resistance to polymyxins poses a significant global public health risk.
  • Acinetobacter baumannii is an opportunistic pathogen known for its resistance to multiple antibiotics.

Purpose of the Study:

  • To identify specific mechanisms of polymyxin resistance in Acinetobacter baumannii.
  • To elucidate the role of lipid A modification in conferring polymyxin resistance.
  • To investigate the regulatory pathways controlling polymyxin resistance genes.

Main Methods:

  • Genetic analysis of Acinetobacter baumannii strains.
  • Biochemical assays to study lipid A modification.
  • Gene expression studies to understand regulatory networks.

Main Results:

  • The Acinetobacter baumannii NaxD deacetylase was identified as a key enzyme in lipid A modification.
  • NaxD activity directly leads to increased resistance to polymyxin antibiotics.
  • The expression of the naxD gene is regulated by the sensor kinase PmrB.
  • This study is the first to describe a PmrB-regulated gene contributing to polymyxin resistance in A. baumannii.

Conclusions:

  • NaxD-mediated lipid A modification is a critical mechanism for polymyxin resistance in A. baumannii.
  • The PmrB-NaxD regulatory pathway is essential for polymyxin resistance.
  • Targeting NaxD presents a promising strategy to overcome polymyxin resistance and restore antibiotic efficacy.

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