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Targetting efflux pumps to combat antibiotic resistance

Primary Supervisor: Dr Jessica Blair, Institute of Microbiology and Infection

Secondary supervisor: Dr Michelle Buckner

PhD project title: Targetting efflux pumps to combat antibiotic resistance

University of Registration: University of Birmingham

Project outline:

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 (Blair, Richmond et al. 2014). 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 research in Dr Blair’s lab is focused on

  1. Investigating the involvement of RND efflux pumps in antimicrobial resistance
  2. Understanding how efflux pumps are regulated.
  3. Understanding the role of the periplasmic adaptor protein component of efflux complexes with the aim of developing inhibitors of efflux pumps.
  1. Investigating the sequence conservation of efflux pumps at a species level.

Dr Blair is very happy to discuss a potential mini-project or PhD project in any of these areas.

The project will likely include a combination of molecular microbiology, bacterial physiology, structural biology and bioinformatics.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology

Techniques that will be undertaken during the project:

The project will likely include a combination of:

  • Molecular microbiology
  • Bacterial physiology
  • Structural biology and bioinformatics

Contact: Dr Jessica Blair, University of Birmingham