Context-Dependent Acquisition of Antimicrobial Resistance Mechanisms

Abstract

Natural transformation is a process whereby bacteria actively take up free DNA from the environment while in a physiological state termed competence. Uptaken DNA is then recombined into the recipient’s genome or reconverted into extra-chromosomal genetic elements. The inducing stimuli for competence vary widely between transformable species and competence induction is affected by a host of abiotic factors found in bacterial environments. Natural transformation is recognised to be responsible for the dissemination of antimicrobial resistance genes both within and between species, contributing to the global antimicrobial resistance crisis threatening modern medicine. Despite being the first mechanism of horizontal gene transfer discovered, the evolutionary benefits of natural transformation are still under debate. This thesis is comprised of four standalone research chapters which aimed 1) to determine if chemotherapeutic compounds affect the transformation frequencies of transformable bacteria. This provides important information which can have implications on the contraction of a life-threatening infection in cancer patients. 2) to determine if other environmentally relevant bacteria affect the transformation frequencies of transformable bacteria. Understanding the contexts under which bacteria transform in their natural environments can help us to predict the spread of antimicrobial resistance mechanisms via natural transformation. 3) to produce a resource of genomic information for the scientific community, allowing researchers to improve our understanding of the Acinetobacter genus. And 4) to determine if environmentally relevant bacteria affect the transformation frequencies of transformable bacteria to find evidence for the sex hypothesis for natural transformation. This was performed by using biotic interactions as a selection pressure and DNA from a range of related species as a substrate for transformation. Together, these chapters provide information about the contexts under which transformation is both regulated and selected for in realistic environmental contexts. Enhancing our understanding of how and when bacteria naturally transform, in both natural and clinical environments, can help us to monitor and establish preventative measures to limit the spread of antimicrobial resistance genes between bacteria.