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The role of Efflux in Antibiotic Resistance of Clinically Relevant Pathogens

  • Full or part time
    Dr J Blair
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description


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 main research focus of Dr Blair’s lab is understanding the involvement of RND efflux pumps in antimicrobial resistance and better understanding how they contribute to multi-drug resistance in clinical pathogens and how their expression is regulated. The project will include a combination of molecular microbiology, bacterial physiology, structural biology and bioinformatics.


Applicants should have a strong background in Microbiology, particularly bacteriology. They should have a strong commitment to research in antimicrobial resistance and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.

References

Blair, J. M., G. E. Richmond and L. J. Piddock (2014). “Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance.” Future Microbiol 9(10): 1165-1177.

Helen E Smith and Jessica M A Blair. Redundancy in the periplasmic adaptor proteins AcrA and AcrE provides resilience and an ability to export substrates of multidrug efflux. Journal of Antimicrobial Chemotherapy. 2014. 69(4): 982-987.
Blair, J. M., M. A. Webber, A. J. Baylay, D. O. Ogbolu and L. J. Piddock (2015). “Molecular mechanisms of antibiotic resistance.” Nat Rev Microbiol 13(1): 42-

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