Antibiotic resistance and Acinetobacter

Darby, Elizabeth M (2023). Antibiotic resistance and Acinetobacter. University of Birmingham. Ph.D.

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Abstract

Antimicrobial resistance is a huge global health burden, where bacterial infections are becoming more difficult to treat. In the England and Wales, bloodstream infections can be caused by a number of bacteria including either A. baumannii or A. lwoffii. This work is a comprehensive comparison between these two species of the Acinetobacter genus, focusing on their antibiotic susceptibility, resistance mechanisms, and ability to cause infection, where A. baumannii was more virulent both in vitro and in vivo, when compared with A. lwoffii. A. lwoffii was also more susceptible to antibiotic treatment and this was due to a lack of acquired resistance genes and a reduced capacity to develop resistance mutations. Efflux pumps, known to confer antibiotic resistance, were found to be fewer in A. lwoffii genomes compared to A. baumannii. Furthermore, A. lwoffii encoded a higher number of DNA defense systems, which, combined with a reduced efflux capacity, potentially explains the scarcity of antibiotic resistance genes in its genome and lack of resistant mutations.
This work also evaluated the Acinetobacter genus as a whole and found that infection- causing species often possessed a greater number of efflux pumps. AdeIJK was identified as a conserved feature across Acinetobacter species, indicating its significance in cellular functions and membrane modulation.
Therefore, this research shows that even two closely-related species that cause similar infections can have dramatically different susceptibility profiles to antibiotics and this is underpinned by a variety of mechanisms, including efflux. By understanding why certain bacterial species rapidly develop antibiotic resistance and the mechanisms of this in comparison to susceptible organisms, will enable researchers to limit the development of antibiotic resistance and find novel antibiotics to treat infections and improve public health.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):