Energetics and mechanisms of substrate transport by the MATE transporter PfMATE
type: CreativeWork
description: Multidrug resistance of microbial pathogens and cancers is a significant global challenge, imposing substantial economic and social burdens. Organisms ranging from bacteria to mammals can develop resistance to previously effective drugs, which compromises the therapeutic outcomes. The misuse and over-prescription of antimicrobials contribute significantly to this problem, undermining the efficacy of treatments for routine infections and compromising the success of critical medical interventions. Additionally, the widespread occurrence of multidrug resistant pathogens has raised alarms due to their severe consequences, which include higher rates of treatment failures, prolonged hospital stays, and increased mortality. Multidrug transporters play a critical role in the multidrug resistance. These efflux pumps can use the energy derived from ATP hydrolysis and/or electrochemical ion gradients to actively remove structurally unrelated drugs, such as antimicrobials and anticancer drugs, from cells. PfMATE, a MATE (multidrug and toxic compound extrusion) transporter, has gained wide attention for being one of the best characterised ion-coupled multidrug transporters with both outward-facing and inward-facing protein conformations determined. Although advanced techniques have brought insights into the structural features of PfMATE, the intricate details of its transport mechanism, including substrate selection, ion coupling, ion-drug stoichiometry, and the role of lipids, have remained elusive. In this PhD project, I employed lactococcal cells to measure ethidium transport by PfMATE. This method involved the use of various ionophores to manipulate the composition and magnitude of proton motive forces across the plasma membrane of these cells. My findings indicate that PfMATE mediates electroneutral ethidium+ /H + antiport independent of membrane potential. Alongside with mutagenesis work, this investigation not only identified the essential carboxylates integral to PfMATE …
abstract: Multidrug resistance of microbial pathogens and cancers is a significant global challenge, imposing substantial economic and social burdens. Organisms ranging from bacteria to mammals can develop resistance to previously effective drugs, which compromises the therapeutic outcomes. The misuse and over-prescription of antimicrobials contribute significantly to this problem, undermining the efficacy of treatments for routine infections and compromising the success of critical medical interventions. Additionally, the widespread occurrence of multidrug resistant pathogens has raised alarms due to their severe consequences, which include higher rates of treatment failures, prolonged hospital stays, and increased mortality. Multidrug transporters play a critical role in the multidrug resistance. These efflux pumps can use the energy derived from ATP hydrolysis and/or electrochemical ion gradients to actively remove structurally unrelated drugs, such as antimicrobials and anticancer drugs, from cells. PfMATE, a MATE (multidrug and toxic compound extrusion) transporter, has gained wide attention for being one of the best characterised ion-coupled multidrug transporters with both outward-facing and inward-facing protein conformations determined. Although advanced techniques have brought insights into the structural features of PfMATE, the intricate details of its transport mechanism, including substrate selection, ion coupling, ion-drug stoichiometry, and the role of lipids, have remained elusive. In this PhD project, I employed lactococcal cells to measure ethidium transport by PfMATE. This method involved the use of various ionophores to manipulate the composition and magnitude of proton motive forces across the plasma membrane of these cells. My findings indicate that PfMATE mediates electroneutral ethidium+ /H + antiport independent of membrane potential. Alongside with mutagenesis work, this investigation not only identified the essential carboxylates integral to PfMATE …
author: Bai, Boyan
language: eng
keywords: multidrug resistance, MATE transporter, PfMATE
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/6c1a503a-e281-455a-b779-7a18234d80f5/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-12-31
date modified: 2026-07-22T22:24:13Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.113342