Dissecting the molecular mechanisms of antibiotic resistance in bacterial pathogens
About the Project
Antibiotics make possible the treatment and cure of life-threatening bacterial infections. Since their introduction in the middle years of the 20th Century, they have added ~10 years to the human lifespan, and have become a cornerstone of modern medicine. Unfortunately, the utility of these agents is being rapidly eroded as pathogenic bacteria evolve to resist their effects. Compounding the issue, in the last 50 years only two truly novel antibiotic classes have been developed for treating serious bacterial infection. If this problem is not addressed as a matter of urgency, 300 million people worldwide are expected to die prematurely between now and 2050, and antimicrobial resistance (AMR) will overtake cancer as a cause of death.
The O’Neill laboratory at Leeds is actively pursuing several complementary approaches to better understand and address this phenomenon, and has a specific focus on understanding the mechanisms that allow ’superbugs’ to resist the effects of antibiotics. Study of these mechanisms not only provides important fundamental insights into the biology of AMR, but also offers valuable strategic intelligence to inform the discovery of new generations of antibiotics capable of overcoming or circumventing existing resistance mechanisms. We are currently looking for a talented and motivated PhD candidate to help us elucidate the molecular detail of antibiotic resistance mechanisms found in major human pathogens such as Staphylococcus aureus. The appointed student will gain cutting-edge, multidisciplinary training in bacteriology, molecular biology and allied disciplines (e.g. bioinformatics, biochemistry).
Please see the O’Neill lab website for more information about what we do, and links to our published work:
Funding Notes
This project is open to applicants who have personal funding to support their own studies or who have a sponsor who will cover these costs.
References
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
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
Wilson DN, Hauryliuk V, Atkinson GC, O'Neill AJ (2020). Target protection as a key antibiotic resistance mechanism. Nature Reviews Microbiology, 18: 637-648
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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