Active Efflux Leads to Heterogeneous Dissipation of Proton Motive Force by Protonophores in Bacteria

• Type of Material: Article
• Authors: Dai Le, Emory University; Ekaterina Krasnopeeva, University of Edinburgh; Faris Sinjab, University of Edinburgh; Teuta Pilizota, University of Edinburgh; Minsu Kim, Emory University
• Language: English
• Date: 2021-07-13
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Le et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/mBio.00676-21
• Title of Journal or Parent Work: mBio
• Volume: 12
• Issue: 4
• Keywords: protonophore; single-cell microscopy; proton motive force; efflux pumps; bacterial physiology; cell-to-cell heterogeneity
• Research Categories: Physics, General

Abstract

Various toxic compounds disrupt bacterial physiology. While bacteria harbor defense mechanisms to mitigate the toxicity, these mechanisms are often coupled to the physiological state of the cells and become ineffective when the physiology is severely disrupted. Here, we characterized such feedback by exposing Escherichia coli to protonophores. Protonophores dissipate the proton motive force (PMF), a fundamental force that drives physiological functions. We found that E. coli cells responded to protonophores heterogeneously, resulting in bimodal distributions of cell growth, substrate transport, and motility. Furthermore, we showed that this heterogeneous response required active efflux systems. The analysis of underlying interactions indicated the heterogeneous response results from efflux-mediated positive feedback between PMF and protonophores’ action. Our studies have broad implications for bacterial adaptation to stress, including antibiotics.