Discovery of novel antimicrobial agents and resistance mechanisms in Halophilic Archaea

Abstract

This work aimed to examine whether halophilic archaea may act as a reservoir for antimicrobial resistance genes in extreme environments and their potential to be a source of new antimicrobial agents. The extremely halophilic archaea Halorubrum saccharovorum CSM-52, isolated from Kilroot salt mine in Northern Ireland, was investigated for the presence of resistance mechanisms, specifically active efflux pumps and the potential of the involvement of these pumps in their innate resistance to antimicrobials. Separately, H. saccharovorum was serially exposed to sublethal concentrations of ciprofloxacin in order to examine its adaptive response and ability to develop antibiotic resistance under antimicrobial stress. The metagenome of stalactite structures formed within the Triassic halite of Kilroot salt mine were subjected to metagenomic mining using a novel bioinformatic pipeline, AMPLY, for the discovery antimicrobial peptide sequences within this unique environment. The top hit sequences were synthesized and examined for their antimicrobial activity against clinically relevant bacteria, Candida albicans and representative haloarchaea.

Thesis embargoed until 31 July 2027.

Date of Award	Jul 2022
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Hashemite University
Supervisor	Brendan Gilmore (Supervisor) & Tim Skvortsov (Supervisor)