How does a phenothiazine enhance the killing of intracellular bacteria including mycobacteria?
Phenothiazines have been shown to inhibit the transport of K+ from external to internal cellular compartments such as transport channels of cardiac Kir2.1 cells and red blood cells78 80 and between intracellular compartments (e.g. diencephalic neurons, rat liver mitochondria).81,82 They also inhibit the binding of calcium to calmodulin, the calcium binding protein of mammalian cells.83 The binding of calcium to calmodulin-like proteins of bacteria has been amply demonstrated.84 93 The inhibition of calcium access to Ca2+-dependent ATPase inhibits transport processes such as those performed by influx and efflux pumps.94 96 Because phenothiazines inhibit access to calcium, they inhibit the activity of calcium-dependent ATPase, and hence the transport processes.94 101 Bacteria as well as mammalian cells contain efflux pumps that extrude noxious agents from the periplasm and cytoplasm of the former102 and from the cytoplasm of the latter.103 Understanding the effects of a phenothiazine on
