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

Infections involving slow-growing and persistent bacteria, includingMycobacterium tuberculosisand biofilms, are difficult to treat. Here, Hurdle and colleagues argue that developing antibiotics to target the bacterial membrane and membrane functions is a promising approach for the treatment for these difficult-to-treat infections. 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.