The role of Efflux in Antibiotic Resistance of Clinically Relevant Pathogens

About the Project

Antibiotics underpin all of modern medicine; they are used to treat bacterial infections, and to prevent infections after surgery and in patients with a suppressed immune system such as those undergoing cancer chemotherapy or organ transplantation. However, bacteria are able to employ various mechanisms to resist the action of antibiotics and the number of infections caused by bacteria that are resistant to antibiotics is increasing globally. This means that bacterial infections are becoming harder to treat. In fact, antibiotic resistant infections kill 700,000 people worldwide every year and this number is rising annually. Additionally, there is a lack of new antibiotics being developed to replace those that we can no longer use.

Bacteria become resistant to antibiotics in many ways but one important mechanism is via multi-drug efflux pumps (Darby et al., 2023). These are pumps, found in the membranes of bacterial cells, that can pump antibiotics out of bacterial cells. This reduces the amount of drug inside the bacteria allowing them to survive at higher drug concentrations and therefore, conferring antibiotic resistance. These pumps can export many different classes of antibiotic so the bacteria are resistant to many drugs at the same time, known as multi-drug resistant (MDR). The Resistance Nodulation Division (RND) family of efflux pumps confer antibiotic resistance to many human pathogens, including the foodborne pathogen Salmonella.

The main research focus of Dr Blair’s lab is understanding the involvement of RND efflux pumps in antimicrobial resistance. In particular, we are interested in how efflux is controlled and how this impacts the amount of antibiotic that accumulates inside bacterial cells.

The team is a welcoming, inclusive environment that focuses on student development and learning while working on important and exciting problems connected to AMR.

This project will involve mastering the measurement of many of aspects of microbial physiology including antimicrobial susceptibility, plasmid conjugation, efflux rates and intracellular antimicrobial accumulation. This project will involve training in a range of microbiology and molecular biology skills, likely to include flow cytometry, FACS, bacterial culture, genetic engineering, plasmid conjugation and persistence assays, sequencing and analysis.

References

1. Darby, E.M., Trampari, E., Siasat, P. et al. Molecular mechanisms of antibiotic resistance revisited. Nat Rev Microbiol 21, 280–295 (2023). DOI:10.1038/s41579-022-00820-y
2. Siasat and Blair, 2024. Microbial Primer: Multidrug efflux pumps. Microbiology. doi:10.1099/mic.0.001370

Project supervisors

Professor Jessica Blair PhD