Interplay between nitric oxide and antimicrobial susceptibility in Escherichia coli

Miller, Joy (2017) Interplay between nitric oxide and antimicrobial susceptibility in Escherichia coli. Master of Science by Research (MScRes) thesis, University of Kent,. (Full text available)

Abstract

Due to the emergence of widespread antibiotic resistance in bacterial pathogens, a greater understanding of bacterial responses to current drugs is required. A recent study reports that aerobic respiration is required for correct function of bactericidal antibiotics. Intriguingly, human macrophages and neutrophils produce the respiratory inhibitor nitric oxide in response to bacterial infection, so it would seem that the host immune system is impairing the ability of antibiotics to work effectively. To test this hypothesis, Escherichia coli strains were exposed to GSNO, a nitric oxide donor, and were subsequently exposed to antibiotics. Increasing the concentration of NO resulted in a dose-dependent attenuation in antibiotic efficacy, which is consistent with our hypothesis. Previous work in the Shepherd lab has reported the respiratory oxidase cytochrome bd-I as being resistant to NO, so we hypothesised that expression of this respiratory complex would sensitise E. coli to antibiotics when grown in the presence of NO. Experiments with cytochrome bd-I knockout strains and a NO donor were performed to test this hypothesis. This work highlights discrepancies between minimal lethal concentrations in the presence and absence of NO, which has obvious implications for our understanding of antibiotic efficacy during infection.

Item Type: Thesis (Master of Science by Research (MScRes))
Uncontrolled keywords: antibiotic resistance, nitric oxide, E. coli terminal oxidases, cytochrome bd-I
Divisions: Faculties > Sciences > School of Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 12 Apr 2018 15:10 UTC
Last Modified: 23 Apr 2018 14:45 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/66709 (The current URI for this page, for reference purposes)
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