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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
Summary
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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