title: 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.
authors.affiliation: Department of Biology, University of Texas at Arlington, Arlington, Texas 76019, USA. hurdle@uta.edu
authors.forename: Julian G
authors.initials: JG
authors.lastname: Hurdle
authors.forename: Alex J
authors.initials: AJ
authors.lastname: O'Neill
authors.forename: Ian
authors.initials: I
authors.lastname: Chopra
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000166:cytology* / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy*; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents