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Intracellular pH homeostasis and metabolic processes in microbes refer to the integrated physiological systems used by bacteria and fungi to maintain a stable internal pH despite external environmental fluctuations. Microbes utilize a variety of mechanisms, including proton-translocating F1F0-ATPases, cation/proton antiporters (such as NhaA), and metabolic pathways that consume or produce protons, to survive in diverse niches (Booth, 1985; Krulwich et al., 2011). These processes are essential for maintaining the proton motive force (PMF) required for ATP synthesis, nutrient uptake, and flagellar rotation. In pharmacology, these systems are targeted by antimicrobial agents like bedaquiline, which inhibits mycobacterial ATP synthase, or weak organic acids used as preservatives that acidify the cytoplasm (Andries et al., 2005; Slonczewski et al., 2009). Because this entry describes a broad biological process involving multiple proteins and pathways rather than a single molecular entity, it is categorized as a physiological system rather than a discrete therapeutic target.
Disruption of the proton motive force (PMF), inhibition of proton-translocating ATPases, or uncoupling of oxidative phosphorylation to collapse the transmembrane pH gradient and deplete cellular energy stores.
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