Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections
- PMID: 21164535
- PMCID: PMC3496266
- DOI: 10.1038/nrmicro2474
Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections
Abstract
Persistent infections involving slow-growing or non-growing bacteria are hard to treat with antibiotics that target biosynthetic processes in growing cells. Consequently, there is a need for antimicrobials that can treat infections containing dormant bacteria. In this Review, we discuss the emerging concept that disrupting the bacterial membrane bilayer or proteins that are integral to membrane function (including membrane potential and energy metabolism) in dormant bacteria is a strategy for treating persistent infections. The clinical applicability of these approaches is exemplified by the efficacy of lipoglycopeptides that damage bacterial membranes and of the diarylquinoline TMC207, which inhibits membrane-bound ATP synthase. Despite some drawbacks, membrane-active agents form an important new means of eradicating recalcitrant, non-growing bacteria.
References
-
- Coates AR, Hu Y. Targeting non-multiplying organisms as a way to develop novel antimicrobials. Trends Pharmacol Sci. 2008;29:143–150. This review provides an excellent description of why antibiotics are needed against slow and non-growing organisms. - PubMed
-
- Levin BR, Rozen DE. Non-inherited antibiotic resistance. Nat Rev Microbiol. 2006;4:556–562. Through mathematical modeling and computer simulations, this paper describes how non-inherited resistance could extend antibiotic treatment duration, cause treatment failure and lead to the emergence of genetic resistance. - PubMed
-
- Chopra I, Hesse L, O’Neill AJ. Exploiting current understanding of antibiotic action for discovery of new drugs. J Appl Microbiol. 2002;92 (Suppl):4S–15S. - PubMed
-
- Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318–1322. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
