Disrupting the regulatory mechanisms that allow hospital acquired infections to resist antibiotic therapy.
The discovery of penicillin over 90 years ago and its subsequent uptake by healthcare systems around the world revolutionised global health and wellbeing. It marked the beginning of a golden age in antibiotic discovery with new classes of antibiotics being routinely discovered and saving millions of lives annually. However, towards the end of the last century, the rate of discovery slowed to a near standstill. This lack of discovery has been compounded by the rapid emergence and spread of bacterial pathogens that exhibit multidrug resistance threatening the sustainability of healthcare systems globally.
Acinetobacter baumannii is a Gram negative coccobacillus that is associated with hospital-acquired infections worldwide. It is an opportunistic pathogen that can colonise a range of anatomical sites in immune-compromised individuals leading to a variety of life-threatening clinical complications. ~2% of all healthcare-associated infections in Europe and USA are caused by this pathogen. The greatest concern associated with this pathogen however is that between 45 - 70% of isolates exhibit multidrug resistance; rates that are significantly higher than those observed for other Gram negative pathogens such as Pseudomonas aeruginosa.
This proposed research project aims to identify compounds that can disrupt the underlying regulatory mechanisms that allow Acinetobacter baumannii to resist treatment and persist in the hospital environment. We will use a combination of custom-designed biosensors, invertebrate model organisms, high throughput screening and artificial models of infection persistence to identify potential new antimicrobials. The mechanism of action of these candidates will then be explored using a range of classical microbiology and genetic approaches. To determine specificity, the impact of these new antimicrobials on the native microbiome will also be investigated using next-generation sequencing technologies.
How to apply
If you are interested in applying for the above PhD topic please follow the steps below:
- Contact the supervisor by email or phone to discuss your interest and find out if you woold be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
- Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
- Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.
This is a self funded topic
Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.
Dr Ronan McCarthy
- Ronan gained his Bachelor of Science in Genetics with first class honours from University College Cork, Ireland in 2010 and was awarded the title of College Scholar. In autumn 2010, Ronan was awarded an Irish Research Council PhD Scholarship to study novel biofilm inhibition strategies against the opportunistic pathogen Pseudomonas aeruginosa
in the lab of Professor Fergal O’Gara. In 2014, Ronan joined the research group of Professor Alain Filloux at the MRC Centre for Bacteriology and Infection at Imperial College London. As a Postdoctoral Research Associate, Ronan interrogated the second messenger signalling cascades that govern the biofilm mode of growth in Pseudomonas aeruginosa
and Agrobacterium tumefaciens
. Following on from his time at Imperial College Ronan joined the Microbiology Department at the Animal and Plant Health Agency where he used host transcriptomics and pathway analysis to profile the host response to infection. He joined the Biosciences Division in Brunel University to continue his analysis of the regulatory networks that govern pathogenicity, antimicrobial resistance and biofilm formation in the Gram negative opportunistic pathogens Pseudomonas aeruginosa
and Acinetobacter baumannii.