The biology of antibiotic resistance plasmids

Saw, Howard Thien Hui (2015). The biology of antibiotic resistance plasmids. University of Birmingham. Ph.D.

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Abstract

Plasmids confer genes encoding clinically relevant antibiotic resistance. It was hypothesised that the AcrAB-TolC multidrug resistance efflux pump was required for clinically relevant levels of carbapenem resistance. However, carbapenemase-producing \(Salmonella\) TolC mutants were less susceptible to carbapenems. In the presence of the efflux inhibitor phe-arg- β-naphthylamide (PAβN), wildtype bacteria and 36/86 non-replicate clinical isolates of carbapenem-producing Enterobacteriaceae were ≥4-fold less susceptible to ertapenem. Experimental data suggested that OmpF repression conferred the increased carbapenem MICs. Two blaKPC-encoding plasmids have been isolated in the UK; pKpQIL-UK was found in K. \(pneumoniae\), but its variant, pKpQIL-D2 was also found in other species. Therefore, it was hypothesised that a region of pKpQIL-D2 either conferred a broader plasmid host range and/or a fitness benefit to the host bacterium. Fitness studies measuring growth rates, ability to form biofilm, conjugation frequency and plasmid persistence showed that both plasmids affected the host bacterium but in different ways. Compared to pKpQIL-UK, pKpQIL-D2 did not confer a significant fitness advantage to its host under the conditions tested. RNAsequencing showed both plasmids affected a different set of genes related to metabolism. The understanding of the factor(s) contributing to the persistence and dissemination of successful plasmids may help to control antibiotic resistance.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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