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The bacterial proton-motive force (PMF) is the electrochemical gradient of protons across the cytoplasmic membrane, serving as a fundamental energy source for Staphylococcus aureus (Mitchell, 1961; PubMed: 13771349). It is composed of two distinct components: the electrical potential (delta psi) and the chemical pH gradient (delta pH), which together drive ATP synthesis via the F1Fo-ATPase and power active transport systems (Farha et al., 2013; PubMed: 23949601). In S. aureus, the PMF is also critical for maintaining cell wall integrity and powering multidrug efflux pumps that contribute to antibiotic resistance (Vestergaard et al., 2019; PubMed: 31138625). Many antimicrobial agents, most notably daptomycin, target the cytoplasmic membrane to cause rapid depolarization and the subsequent collapse of the PMF (Silverman et al., 2003; PubMed: 12937121). Because the PMF is a fundamental bioenergetic requirement, its disruption results in an immediate halt in macromolecular synthesis and eventual bacterial cell death (Hurdle et al., 2011; PubMed: 21471956). Targeting the PMF is a validated strategy for treating multidrug-resistant S. aureus infections, though selectivity over host mitochondrial membranes remains a key safety consideration (Farha & Brown, 2019; PubMed: 31515413).
Dissipation of the transmembrane electrical potential (delta psi) and/or the pH gradient (delta pH), leading to the collapse of the electrochemical gradient and subsequent inhibition of ATP synthesis and active transport (Farha & Brown, 2019; PubMed: 31515413).
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