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

Nat Rev Microbiol. 2011 Jan;9(1):62-75. doi: 10.1038/nrmicro2474.

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.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteria / cytology*
  • Bacteria / drug effects*
  • Bacterial Infections / drug therapy*
  • Cell Membrane / drug effects*
  • Cell Membrane / physiology
  • Drug Resistance, Bacterial
  • Gene Expression Regulation, Bacterial / drug effects

Substances

  • Anti-Bacterial Agents