Bacterial transmembrane ion gradient and membrane potential (PMF)

Bacterial transmembrane ion gradients and membrane potential, collectively referred to as the proton motive force (PMF), represent the electrochemical energy stored across the bacterial cytoplasmic membrane (Mitchell, 1961). This gradient consists of two components: the electrical potential (delta-psi) and the transmembrane pH gradient (delta-pH), which together drive essential processes such as ATP synthesis via F1Fo-ATP synthase, active transport of nutrients, and flagellar rotation (PMID: 23147068). In pathogenic bacteria, the PMF is also critical for the operation of multidrug efflux pumps, which contribute significantly to antibiotic resistance (PMID: 29305547). Antibiotics such as daptomycin and polymyxins target this system by inducing membrane depolarization or forming pores, leading to a rapid loss of ion gradients and subsequent metabolic collapse (PMID: 15105401, PMID: 25130014). Because the PMF is fundamental to bacterial life, its dissipation is a highly effective bactericidal mechanism, even against non-dividing cells. However, a major challenge in targeting these gradients is ensuring selectivity to avoid damaging host mitochondrial membranes, which share evolutionary origins and bioenergetic principles with bacteria.

Other names

Proton motive forceElectrochemical gradientBacterial membrane potentialDelta-psiDelta-pH

Disruption of the electrochemical gradient through pore formation, ionophore activity, or membrane depolarization, leading to metabolic exhaustion and cell death.