Elucidating the molecular mechanisms of intrinsic antibiotic resistance in bacterial pathogens


   Faculty of Biological Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Antibiotics make possible the treatment and cure of life-threatening bacterial infections and have added over a decade to the average human lifespan. Unfortunately, the utility of these drugs is being rapidly eroded as pathogenic bacteria evolve to resist their effects; in 2019, antimicrobial resistance (AMR) killed ~1.3 million people worldwide, and this figure is set to rise to 10 million by 2050. The O’Neill laboratory at Leeds is actively pursuing several complementary approaches to better understand and address this phenomenon, with a major focus on understanding the mechanisms that allow ’superbugs’ to resist the effects of antibiotics. 

Studies into antibiotic resistance mechanisms have typically focused on acquired resistance – in other words, evolved traits that become selected in bacteria by antibiotic exposure. However, many bacteria are inherently resistance to particular antibiotic classes, a phenomenon known as intrinsic resistance. The latter is currently under-studied, though it has become clear that analysis of such intrinsic resistance mechanisms can offer profound fundamental insights into the biology of AMR and provide valuable strategic intelligence to inform the discovery of newer generations of antibiotics. This studentship will investigate the genetic and biochemical basis for intrinsic resistance to a variety of important antibacterial drugs in key pathogenic bacteria, employing a suite of cutting-edge approaches in molecular biology to do so. Please see reference I below for an example of intrinsic resistance and the kinds of tools we have at our disposal to study it.

Please see the O’Neill lab website for more information about what we do, and links to our published work:

https://biologicalsciences.leeds.ac.uk/molecular-and-cellular-biology/staff/119/professor-alex-o-neill

Eligibility: 

You should hold a first degree equivalent to at least a UK upper-second class honours degree or a MSc degree in a relevant subject.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in an IELTS test is:

  • British Council IELTS - score of 6.0 overall, with no element less than 5.5

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).
  • Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert
Biological Sciences (4)

Funding Notes

This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.

References

I. Mohamad M, Nicholson D, Saha CK, Hauryliuk V, Edwards TA, Atkinson GC, Ranson NA, O’Neill AJ (2022). Sal-type ABC-F proteins: intrinsic and common mediators of pleuromutilin resistance by target protection in staphylococci. Nucleic Acids Research, 50: 2128-2142
II. Crowe-McAuliffe C, Murina V, Turnbull KJ, Kasari M, Mohamad M, Polte C, Takada H, Vaitkevicius K, Johansson J, Ignatova Z, Atkinson GC, O’Neill AJ, Hauryliuk V, Wilson DN (2021). Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens. Nature Communications, 12: 3577
III. Wilson DN, Hauryliuk V, Atkinson GC, O'Neill AJ (2020). Target protection as a key antibiotic resistance mechanism. Nature Reviews Microbiology, 18: 637-648
IV. Kime L, Randall CP, Banda FI, Coll F, Wright J, Richardson J, Empel J, Parkhill J, O'Neill AJ. 2019. Transient Silencing of Antibiotic Resistance by Mutation Represents a Significant Potential Source of Unanticipated Therapeutic Failure. mBio, 10: e01755-19

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