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Polymyxins: Mode of Action.

Zhifeng Li1, Tony Velkov2

  • 1State Key Laboratory of Microbial Technology, Shandong University, Qingdao Campus, Qingdao, Shandong, People's Republic of China.

Advances in Experimental Medicine and Biology
|August 1, 2019
PubMed
Summary

Polymyxin antibiotics are being re-examined due to rising superbug resistance. This work reviews their primary action, bacterial responses, and secondary mechanisms to guide future antibiotic development.

Keywords:
Free radicalLPSOuter membrane remodellingPolymyxinType II NADH-quinone oxidoreductase

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Area of Science:

  • Microbiology
  • Pharmacology
  • Infectious Diseases

Background:

  • The antibiotic development pipeline is facing challenges, with a notable lack of new drugs targeting Gram-negative bacteria.
  • The rise of multi-drug resistant (MDR) Gram-negative pathogens, often termed 'superbugs', necessitates urgent solutions.
  • Polymyxin lipopeptide antibiotics, previously sidelined, are experiencing a resurgence in interest due to their efficacy against these resistant strains.

Purpose of the Study:

  • To consolidate current knowledge on the primary mode of action of polymyxin antibiotics.
  • To explore recent advancements in understanding how bacteria respond to polymyxin treatment.
  • To investigate potential secondary mechanisms of action for polymyxins.

Main Methods:

  • Literature review and synthesis of existing research on polymyxin antibiotics.
  • Analysis of studies detailing bacterial cell envelope interactions and resistance mechanisms.
  • Examination of data on polymyxin's effects beyond direct bacterial killing.

Main Results:

  • Polymyxins primarily act by disrupting the bacterial outer membrane of Gram-negative bacteria.
  • Bacterial cells exhibit complex responses to polymyxin exposure, including alterations in cell wall synthesis and efflux pump activity.
  • Emerging evidence suggests secondary mechanisms contributing to polymyxin's overall antimicrobial effect.

Conclusions:

  • A comprehensive understanding of polymyxin's multifaceted action is crucial for their effective clinical application.
  • Further research into bacterial responses and secondary mechanisms can inform the development of next-generation polymyxins.
  • Optimizing polymyxin use and combating antibiotic resistance requires a deep knowledge of their mode of action.