scholarly journals Active maintenance of proton motive force mediates starvation-induced bacterial antibiotic tolerance in Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Miaomiao Wang ◽  
Edward Wai Chi Chan ◽  
Yingkun Wan ◽  
Marcus Ho-yin Wong ◽  
Sheng Chen

AbstractRecent evidence suggests that metabolic shutdown alone does not fully explain how bacteria exhibit phenotypic antibiotic tolerance. In an attempt to investigate the range of starvation-induced physiological responses underlying tolerance development, we found that active maintenance of the transmembrane proton motive force (PMF) is essential for prolonged expression of antibiotic tolerance in bacteria. Eradication of tolerant sub-population could be achieved by disruption of PMF using the ionophore CCCP, or through suppression of PMF maintenance mechanisms by simultaneous inhibition of the phage shock protein (Psp) response and electron transport chain (ETC) complex activities. We consider disruption of bacterial PMF a feasible strategy for treatment of chronic and recurrent bacterial infections.

2022 ◽  
Author(s):  
Michael Zemel ◽  
Alessia Angelin ◽  
Prasanth Potluri ◽  
Douglas Wallace ◽  
Francesca Fieni

Mitochondria generate ATP via coupling the negative electrochemical potential (proton motive force, Capital Greek (Deltap), consisting of a proton gradient (Capital Greek DeltapH+) and a membrane potential (Capital Greek Psim) across the respiratory chain, to phosphorylation of adenosine diphosphate nucleotide. In turn, DeltapH+ and Capital Greek Psim, are tightly balanced by the modulation of ionic uniporters and exchange-diffusion systems which preserve integrity of mitochondrial membranes and regulate ATP production. Here, we provide direct electrophysiological, pharmacological and genetic evidence that the main mitochondrial electrophoretic pathway for monovalent cations is associated with respiratory complex I, contrary to the long-held dogma that only H+ gradients are built across proteins of the mammalian electron transport chain. Here we propose a theoretical framework to describe how monovalent metal cations contribute to the buildup of H+ gradients and the proton motive force, extending the classical Mitchellian view on chemiosmosis and vectorial metabolism. Keywords: mitochondrial electrogenic transport, chemiosmotic theory, vectorial metabolism, whole-mitochondria electrophysiology.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Albert Byungyun Jeon ◽  
David F. Ackart ◽  
Wei Li ◽  
Mary Jackson ◽  
Roberta J. Melander ◽  
...  

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