New drugs to tackle AMR
GW4 community leads
University of Bath: Maisem Laabei
University of Bristol: Seána Duggan, Jonathan M. Tyrrell
Cardiff University: Michaela Serpi (PI)
University of Exeter: Tobias Bergmiller, Remy Chait
In this project, we will develop novel antimicrobial compounds to treat Gram-positive bacterial infections combining our expertise in drug discovery, organic synthesis, microbiology and molecular microbial ecology and evolution to enhance the ability of the agents to kill bacteria and interfere with biofilm formation.
The global challenges research area which we would like to address is “Health, demographic change and wellbeing”. Specifically, we will build capacity to treat and manage bacterial infection.
AMR is expected to cause 10,000,000 deaths a year by 2050, with an associated $1 trillion global cost. Staphylococcus aureus is an organism of particular concern in the context of AMR, due to its ability to cause infection in, and adapt to, diverse host niches. Antimicrobial resistant strains of S. aureus (e.g. MRSA), cause a significant number of life-threatening hospital and community-acquired infections. It is estimated that up to 80% of S. aureus infections are caused by biofilms- that is a community of cells attached to a substrate (i.e. catheter) or each other, and embedded within a matrix of extracellular substance. Biofilms also pose a therapeutic impediment and are notoriously difficult to treat. As such, S. aureus is designated by the WHO as a high priority pathogen for development of new antibiotics. With an increasing number of vulnerable people in society, it is imperative to discover new drugs effective against organisms such as S. aureus.
The community arose from a Seed Corn project developed via the 2020 Crucible. Using the Generator Funds they have successfully established a collaboration across all GW4 institutes dedicated to the development of antimicrobial compounds to inhibit important human pathogens. The team have combined their complementary expertise in medicinal chemistry, molecular microbiology and antibiotic resistance to develop novel anti-bacterials, using a suite of gold-standard methodologies, optimised in GW4 laboratories. Laboratory work across all four GW4 universities identified a novel compound with enhanced antimicrobial activity: work is ongoing to explore the utility of this compound and understand its mode of action. The community have secured a PhD Studentship to continue this work and a manuscript is underway.
The core team are now part of the GW4 AMR Alliance: Michaela Serpi is GW4 AMR Champion for Cardiff and all are part of the GW4 AMR ECR/PGR Network, where Maisem Laabei and Jonathan Tyrell are the ECR representatives on the GW4 AMR Steering Committee.
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