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Disrupting biofilm formation in nosocomial pathogens

A biofilm by definition is a structured community of bacterial cells enclosed in a self-produced polysaccharide matrix and adherent to an inert or living surface. Bacteria growing in a biofilm are between 10-1,000 times more resistant to antibiotic therapy than their planktonic counterparts. As well as an increased tolerance to antibiotics, the biofilm mode of growth offers protection from various environmental challenges such as the innate and the adaptive immune system as well as offering an increased tolerance to disinfection agents. The annual cost for biofilm infections in the USA is estimated to be $94 billion with more than half a million deaths. Due to the clinical importance of biofilms, there is an urgent need to gain a greater understanding of the regulatory cascades that govern their formation and to identify novel compounds that can inhibit their formation.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen associated with high morbidity and mortality in humans. P. aeruginosa is frequently isolated from patients with Cystic Fibrosis, AIDS and burns patients. In 2018, the World Health Organisation identified carbapenem-resistant P. aeruginosa as number two on the priority pathogen list for which there is an urgent need for the development of novel therapeutic strategies due increasing failure of first line antibiotics. P. aeruginosa is notorious for its ability to form biofilms both within the hospital-built environment and in immunocompromised individuals. Given the link between biofilm formation and poor treatment outcomes, the regulatory networks that control biofilm formation in P. aeruginosa are ideal targets for novel therapeutic intervention strategies.

This proposed research project aims to use high through put screening approaches to identify novel compounds that can disrupt the regulatory networks that control biofilm formation in P. aeruginosa. The mechanism of action of these candidates will then be explored using a range of classical microbiology, ‘omics and genetic approaches. Candidates that demonstrate activity against P. aeruginosa will be tested against other clinically relevant Gram-negative pathogens such as Acinetobacter baumannii. A range of model organisms will be used to determine the efficacy of these compounds in vivo.

How to apply

If you are interested in applying for the above PhD topic please follow the steps below:

  1. 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.
  2. 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.
  3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

Good luck!

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%.

Meet the Supervisor(s)

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. In 2021, Ronan was awarded a BBSRC New Investigator Award to study the regulation of desiccation tolerance and biofilm formation in Acinetobacter baumannii and to identify compounds that could disrupt these survival mechanisms.