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.

Antimicrobial defence and persistent infection in insects revisited

“…Persistent infections are causing major problems in the treatment of infectious diseases [39,40]. While more and more mechanisms enabling bacterial cells to persist in antimicrobial environments have been elucidated [41], much less is known about effective treatments of persistent infections.…”

“…While more and more mechanisms enabling bacterial cells to persist in antimicrobial environments have been elucidated [41], much less is known about effective treatments of persistent infections. One important avenue of current research aims to use drugs that target the bacterial membranes [39]. This is based on the notion that it is harder to evolve resistance against drugs targeting the membranes, and also because some recent studies yielded promising results in treating biofilms with membrane-targeting drugs such as lipoglycopeptides and AMPs.…”

Helical antimicrobial polypeptides with radial amphiphilicity

“…They adopt various secondary structures (e.g., α-helix) and can kill a range of bacteria. As AMPs target generic and necessary lipid components of bacterial membranes (1,2) and depend less on specific bacterial metabolic status (3)(4)(5)(6), development of resistance has been slow. Because of this feature, AMPs have attracted significant attention as potential antimicrobial agents clinically.…”

Conventional Antibiotics – Revitalized by New Agents

“…Ways need to be found which slow the emergence of resistance. One possible route could be to use ARBs which target the cell membrane, on the grounds that it may take bacteria longer to develop resistance against combinations which act on the bacterial membrane [66].…”