Bacterial cell membrane and cytoplasmic pH homeostasis

The bacterial cell membrane and cytoplasmic pH homeostasis are fundamental components of bacterial physiology and represent a critical target for antimicrobial agents. The cytoplasmic membrane acts as a selective barrier that maintains the electrochemical gradient, known as the proton motive force (PMF), which is essential for ATP synthesis and nutrient transport (Padan et al., 2005). Cytoplasmic pH homeostasis ensures that the internal environment remains near neutral (pH 7.4–7.8), allowing for the proper function of metabolic enzymes even under environmental stress (Vandal et al., 2008). Drugs such as daptomycin and polymyxins target the membrane directly, causing depolarization or physical disruption that leads to the dissipation of the PMF and rapid cell death (Silver, 2011). Other compounds, including bedaquiline and nitazoxanide, interfere with the bioenergetic machinery or specific pH-regulating proteins like the MarP protease to collapse the pH gradient (Baker et al., 2018). Targeting these systems is particularly effective against non-replicating or persistent bacteria, making them vital in the treatment of chronic infections like tuberculosis. However, the similarity between bacterial and host membrane components can lead to safety concerns such as nephrotoxicity or myopathy.

Other names

Bacterial pH homeostasisIntrabacterial pH regulationCytoplasmic pH maintenanceProton motive force (PMF) maintenanceBacterial membrane integrity

Disruption of membrane integrity, dissipation of the proton motive force (PMF), and inhibition of pH-regulating enzymes or transporters.