Targeting Pseudomonas aeruginosa virulence factors

The emergence of multi-drug antibiotic resistance in many disease-causing bacteria (pathogens) has raised the prospect of a devastating return to the pre-antibiotic era, and, as was highlighted in the UK Governments 2016 review on AMR chaired by Lord Jim O’Neill, it is imperative that new antibiotics are developed to counteract this problem. This also emphasised the need to reduce the use of antibiotics to ensure our current stock lasts longer, while promoting the development of vaccines and alternatives.

One alternative is to block the ability of pathogens to colonise and replicate within the cells of their host target, something they achieve by producing virulence factors that alter the biology of the host to assist the process of colonization. Targeting non-essential virulence mechanisms, rather than growth or viability as antibiotics do, means that the selection pressure for the emergence of resistance to virulence-inhibitors will be reduced.

In this crossdisciplinarity project the successful candidate will use Pseudomonas aeruginosa as a model pathogen to understand the function and regulation of virulence factors to design new anti-virulence strategies. They will develop an understanding of pathogen biology in addition to cutting edge training in molecular microbiology, antimicrobial resistance, biochemical analysis, biophysical techniques, proteomics, and bioinformatics. These skills are essential to the next generation of bioscientist, and the candidate will be further supported in acquiring transferable skills such as written and spoken communication, problem solving and critical thinking and will help train visitors to the lab so s/he can gain skills in knowledge exchange. This combination of skills and experience will make the successful candidate highly employable in both academia and industry.

References

Hutchings, Truman & Wilkinson (2019) ‘Antibiotics: past, present and future’. Current Opinion in Microbiology 51:72-80.

Batey et al (2023) ‘The catechol moiety of obafluorin is essential for antibiotic activity.’ RSC Chemical Biology 4:926-941.

Martinez et al (2019) ‘Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition’. Frontiers in Cellular & Infectious Microbiology 9:74.

Lau et al (2023) ‘Pathogen-associated gene discovery workflows for novel antivirulence therapeutic development’. eBioMedicine 88:104429.