GW4 Crucible 2020 Seed Funding Projects
In Search of new antimicrobials to treat important human pathogens
PI: Maisem Laabei (University of Bath).
Co-Is: Michaela Serpi (Cardiff University), Seána Duggan (University of Bristol), Dhara Malavia (University of Exeter), Mark Stappers (University of Exeter).
The rise of antimicrobial resistance (AMR) due to a rapid emergence of multidrug-resistant (MDR) pathogens and the concurrent reduction in antimicrobial research investment by the pharmaceutical industry – has been forecast to result in ten million deaths per year by 2050 and $1 trillion in accumulative global healthcare costs.
Among MDR, Staphylococci and Candida species are of considerable interest as both are human commensals and opportunistic pathogens. They are leading causes of nosocomial infections and thus represent a serious global health threat. In particular, methicillin-resistant S. aureus(MRSA) has long been of interest as an MDR pathogen associated with high mortality and Candida auris is recently gaining attention as a newly emerging MDR pathogen. Both Staphylococci and Candida cause infections associated with implanted medical devices, a feature promoted by their biofilm-forming capacity. Furthermore, together they enhance each other’s virulence and resistance to antimicrobials. With an increasing number of MDR infection-susceptible people in society (e.g. cancer, ICU and transplant patients), it is imperative to discover new drugs effective against Staphylococci and Candida.
In this project, we aim to develop a functional collaboration that combines our expertise in medicinal chemistry, bacteriology, mycology and antibiotic resistance. In particular our goal is to evaluate two classes of compounds for antimicrobial and anti-biofilm activity against Staphylococci and Candida. We will begin to examine several aspects of compound activity namely, synergistic antimicrobial activity and their effect on bacterial-fungal communities. Finally, we will undertake preliminary studies of their mode of action.