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Proton motive force underpins respiration-mediated potentiation of aminoglycoside lethality in pathogenic Escherichia coli

Webster, Calum M., Woody, Ayrianna, Fusseini, Safura, Holmes, Louis G., Robinson, Gary K., Shepherd, Mark (2022) Proton motive force underpins respiration-mediated potentiation of aminoglycoside lethality in pathogenic Escherichia coli. Archives of Microbiology, 204 . Article Number 120. ISSN 0302-8933. (doi:10.1007/s00203-021-02710-y) (KAR id:91761)


It is well known that loss of aerobic respiration in Gram-negative bacteria can diminish the efficacy of a variety of bactericidal antibiotics, which has lead to subsequent demonstrations that the formation of reactive oxygen species (ROS) and the proton motive force (PMF) can both play a role in antibiotic toxicity. The susceptibility of Gram-negative bacteria to aminoglycoside antibiotics, particularly gentamicin, has previously been linked to both the production of ROS and the rate of antibiotic uptake that is mediated by the PMF, although the relative contributions of ROS and PMF to aminoglycoside toxicity has remained poorly understood. Herein, gentamicin was shown to elicit a very modest increase in ROS levels in an aerobically grown Escherichia coli clinical isolate. The well-characterised uncoupler 2,4-dinitrophenol (DNP) was used to disrupt the PMF, which resulted in a significant decrease in gentamicin lethality towards E. coli. DNP did not significantly alter respiratory oxygen consumption, supporting the hypothesis that this uncoupler does not increase ROS production via elevated respiratory oxidase activity. These observations support the hypothesis that maintenance of PMF rather than induction of ROS production underpins the mechanism for how the respiratory chain potentiates the toxicity of aminoglycosides. This was further supported by the demonstration that the uncoupler DNP elicits a dramatic decrease in gentamicin lethality under anaerobic conditions. Together, these data strongly suggest that maintenance of the PMF is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycosides.

Item Type: Article
DOI/Identification number: 10.1007/s00203-021-02710-y
Uncontrolled keywords: Aminoglycoside, Escherichia coli, Nitric oxide
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Shepherd
Date Deposited: 29 Nov 2021 11:20 UTC
Last Modified: 13 Jan 2022 17:06 UTC
Resource URI: (The current URI for this page, for reference purposes)

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