Hurdle JG, O'Neill AJ, Chopra I et al.Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat Rev Microbiol 9:62-75

Department of Biology, University of Texas at Arlington, Arlington, Texas 76019, USA.
Nature Reviews Microbiology (Impact Factor: 23.57). 01/2011; 9(1):62-75. DOI: 10.1038/nrmicro2474
Source: PubMed


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.

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    • "may quantitatively or qualitatively change their envelope structures as a result of adaptation to developmental signals or environmental cues (Beatty et al., 1994b; Hatch, 1996; Carrasco et al., 2011). The plasticity of the envelope has important implications for the design of control strategies against bacterial infection because of its importance in determining susceptibility to host defenses and antibiotics (Tan et al., 2009; Hurdle et al., 2011). "
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    • "The proposed role of hydrogenase enzymes in M. smegmatis. Depicted is a representation of the mycobacterial electron transport chain, adapted from (Hurdle et al., 2011), and with hydrogenases added. The two oxidative hydrogenases Hyd1 and Hyd2 oxidize hydrogen to provide electrons for the respiratory pathway and adenosine triphosphate (ATP) generation. "
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    • "As discussed by Bolla et al. (2011), an alternate possibility to facilitate the antibiotics to gain access into the cells is to bypass the outer membrane barrier [63]. To bypass the barrier through LPS modifications, chemical facilitators such as detergents, chaotropic agents and polymyxines have been proposed [64, 65]. It is noted that only very limited studies have been reported on the molecular basis of the synergy efficacy between antibiotics and the membrane-active agents and also the study parameters. "
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