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Switching Off Efflux Pumps to Combat Antibiotic Resistance

  • Full or part time
    Dr J Blair
  • Application Deadline
    Friday, January 17, 2020
  • Competition Funded PhD Project (UK Students Only)
    Competition Funded PhD Project (UK Students Only)

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. We now urgently need new antibiotics and novel therapies to treat drug resistant infections.

Bacterial efflux pumps are an important mechanism of antibiotic resistance (Blair et al., 2014). These are protein machines which sit in the bacterial membrane and pump antibiotic molecules directly out of the cell to keep internal concentrations below toxic levels. The aim of this project is to develop a way to turn off production of these pumps to re-sensitize Gram-negative bacteria to existing antibiotics. In this project we will engineer bacteriophage to deliver a factor to turn off production of this important resistance mechanism. The effect on efflux pump production and antibiotic susceptibility will be measured to assess efficacy of the new technology. Finally, an in vivo animal model system (Zebrafish) will be developed to test the impact in a whole animal model.

This is a collaboration between Dr Jessica Blair (University of Birmingham) and Professor Martha Clokie (University of Leicester). The majority of the PhD will be based in Birmingham but the student will also spend time in Prof Clokie’s lab in Leicester. Dr Blair is an expert in mechanisms of antibiotic resistance including bacterial efflux pumps and Prof Clokie is a world expert in bacteriophage biology. During this multidisciplinary project the student will gain expertise from both teams.

Person Specification
Applicants should have a strong background in microbiology. They should have a commitment to research in microbiology, specifically antibiotic resistance, and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in biology, microbiology or related subject.

Funding Notes

Please check the MRC website for full eligibility criteria View Website

References

1. Jessica M. A. Blair, Grace E. Richmond and Laura J. V. Piddock. Multidrug efflux pumps in Gram-negative bacteria: the influence on antibiotic resistance. Future Microbiology. Vol 9, No 10, 1165-77. 2014
2. Jessica M. A. Blair, Mark A. Webber, Alison J. Baylay, David O. Ogbolu and Laura J.V. Piddock. Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology. 13, 42-51. 2014
3. Emily E Whittle, Simon Legood, Ilyas Alav, Tim Overton and Jessica M A Blair. Flow Cytometric Analysis of Efflux by Dye Accumulation. Frontiers in Microbiology. In Press.

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