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Regulating polymyxin resistance in Gram-negative bacteria: roles of two-component systems PhoPQ and PmrAB

Jiayuan Huang1, Chen Li2,3, Jiangning Song2

  • 1Biomedicine Discovery Institute & Department of Microbiology, Monash University, Melbourne 3800, Australia.

Future Microbiology
|April 7, 2020
PubMed

Insights

Polymyxin resistance in Gram-negative bacteria is rising, often mediated by PmrAB and PhoPQ systems. Key mutations in PmrB

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Resistance

Background:

  • Polymyxins (polymyxin B and colistin) are crucial last-resort antibiotics against multidrug-resistant Gram-negative bacteria.
  • Increasing global polymyxin resistance necessitates understanding its regulatory mechanisms.

Purpose of the Study:

  • To review the regulatory mechanisms of two-component systems PmrAB and PhoPQ in mediating polymyxin resistance.
  • To identify critical domains within these systems associated with polymyxin resistance by analyzing mutations.

Main Methods:

  • Literature review of regulatory mechanisms of PmrAB and PhoPQ.
  • Analysis of reported nonsynonymous substitutions in PmrAB and PhoPQ two-component systems.
  • Identification of mutation hotspots within specific protein domains.

Main Results:

  • PmrAB and PhoPQ regulate polymyxin resistance through lipid A modification pathways.
  • Nonsynonymous mutations in PmrAB and PhoPQ are key drivers of polymyxin resistance.
  • Specifically, 71% of resistance-conferring mutations in PmrB were located in the HAMP linker and DHp domains.

Conclusions:

  • Understanding PmrAB and PhoPQ regulatory mechanisms is vital for combating polymyxin resistance.
  • Identifying critical mutation domains, like those in PmrB, aids in predicting and potentially counteracting resistance.
  • This knowledge can inform strategies to mitigate the emergence of polymyxin resistance.
Keywords:
PhoPQPmrABlipid A modificationpolymyxin resistancetwo-component system

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