Antibiotic Resistance Selection in the Presence of Metals and Antimicrobials

Abstract: The external environment is complex: Antibiotics, metals and antimicrobials do not exist in isolation but in mixtures. Human activities such as animal husbandry, fertilization of agricultural fields and human medicine release high amounts these compounds into the environment. The work in this thesis contributes to our understanding of how the selection of bacterial antibiotic resistance can be facilitated by the pollution by metals and antimicrobials. We show that low levels of antibiotics, metals and combinations thereof can lead to the selection of chromosomally encoded antibiotic resistance genes as well as a multidrug resistance plasmid. The underlying genetic and cellular mechanisms of selection identified relate to mutational changes in a plasmid-encoded metal resistance operon, and metal-associated increases in cellular membrane permeability. We further show that exposure to quaternary ammonium compounds can result in cross-resistance to antibiotics following genetic changes in genes related to efflux, membrane synthesis and transcription/translation. Taken together, the work in this thesis suggests that the stewardship of antibiotics should include prudent use of metals and antimicrobials.