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Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections

Julian G Hurdle1, Alex J O'Neill, Ian Chopra

  • 1Department of Biology, University of Texas at Arlington, Arlington, Texas 76019, USA. hurdle@uta.edu

Nature Reviews. Microbiology
|December 18, 2010
PubMed

Insights

Treating persistent bacterial infections requires new antibiotics. Disrupting bacterial membranes offers a promising strategy against dormant, non-growing bacteria, leading to new antimicrobial development.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Persistent bacterial infections are difficult to treat with conventional antibiotics targeting growing cells.
  • Dormant or slow-growing bacteria evade current therapies, necessitating novel antimicrobial approaches.
  • Bacterial membrane integrity and function are crucial for survival, even in non-growing states.

Purpose of the Study:

  • To review emerging strategies for targeting dormant bacteria in persistent infections.
  • To explore the potential of disrupting bacterial membrane function as a therapeutic approach.
  • To highlight the clinical relevance of membrane-active agents against recalcitrant bacteria.

Main Methods:

  • Review of current literature on persistent infections and antimicrobial resistance.
  • Analysis of mechanisms of action for membrane-targeting agents.
  • Evaluation of clinical data for exemplified therapies like lipoglycopeptides and TMC207.

Main Results:

  • Disrupting the bacterial membrane bilayer or integral membrane proteins is a viable strategy against dormant bacteria.
  • Membrane-active agents, such as lipoglycopeptides and diarylquinoline TMC207, show efficacy in treating persistent infections.
  • These agents target essential membrane functions like potential and energy metabolism in non-growing bacteria.

Conclusions:

  • Membrane-active agents represent a significant advancement in combating persistent bacterial infections.
  • Targeting bacterial membranes offers a new therapeutic avenue for eradicating dormant and recalcitrant bacteria.
  • Further development of these agents is crucial for addressing unmet needs in infectious disease treatment.

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