Dynamics of the MacAB-TolC multidrug efflux pump in Acinetobacter baumanni

Project Description

Bacterial multidrug efflux pumps (MEPs) transport antibiotics and contribute to antibiotic resistance. Acinetobacter baumannii (Ab) is a nosocomial pathogen that possesses several MEPs, and is often antibiotic resistant; carbapenem-resistant Ab is a critical priority pathogen which urgently warrants research. Presently, tigecycline and colistin treatment remain among the few effective options for treating carbapenem-resistant Ab. Resistance to both of these last-resort antibiotics in Ab has been associated with the MacAB-TolC multidrug efflux pump, which is also involved in biofilm formation in Ab.
This project will focus on the dynamics of Ab MacAB-TolC, and the impact of resistance-associated mutations during assembly and drug efflux. Students will be invited to select from a variety of techniques including bacterial mutagenesis, enzymology, fluorescence, single-molecule biophysics, and molecular dynamics simulations to build their research project. Insights gained from this project will aid in our understanding of assembly, function, and regulation of this clinically relevant efflux pump in Ab, and MEPs more generally. In addition, this work will help us establish the suitability of MacAB-TolC as a clinically relevant inhibitor target, and develop tools that can be transferred into a drug-discovery platform for high-throughput screening of small-molecule inhibitors.

Funding offered

Yes

$20,000 (MSc); $23,000 (PhD)

The last update was on 6 November 2024. The University reserves the right to modify its projects without notice.