FAILSAFE Fungal Antimicrobial Resistance Innovations for Low & Middle Income Countries: Solutions & Access For Everyone
FAILSAFE Fungal Antimicrobial Resistance Innovations for Low & Middle Income Countries: Solutions & Access For Everyone
Lead applicant
Dr Julio Silva – University of Exeter
Co-applicants
Prof. William Horsnell – University of Exeter
Dr Peter Cook – University of Exeter
Prof. Adrian Brink – University of Cape Town, South Africa
Alisha Chetty – University of Cape Town, South Africa
Prof. Richard Grencis – University of Manchester
Dr Bethany McCann – University of Exeter
Prof. Chris Thornton – ISCA Diagnostics Limited
Geographical focus – Global, but especially LMICs
Research Theme – Microbial Pathogenesis
Lay summary
Fungal infections are globally both very common and widespread. Some cause only mild symptoms (such as athlete’s foot); yet they can also cause extremely serious diseases where they invade human organs, resulting in over 50% death rates and leading to 2 million deaths a year worldwide. The risk of these serious infections is increasing and the rapid emergence of fungi that are resistance to the antifungals which treat these diseases means the number of deaths are certain to rise further. This has led the World Health Organisation (WHO) to alert the medical community that fungi are critical priority pathogens, with an urgent need to discover new drugs which successfully treat these serious infections. However, there is much we don’t understand about these fungal diseases, especially if having another infection makes individuals more at risk. For instance, both infective fungi and parasitic worms are widespread across the globe and the likelihood of us becoming infected by both at the same is very high, particularly in Lower or Middle income countries (LMICs). Despite this, we don’t understand how these microbes interact when they encounter each other in the human host. As worm infections can protect us from viruses and bacteria, we predict they could also prevent infections from fungal pathogens.
Our initial exploratory data supports this by showing a protein (P43) released by the worm Trichuris muris stops growth of a drug resistant strain of the fungus; Candida auris. We request support from FAILSAFE to explore P43’s potential as a new antifungal drug and whether its mechanism of action is distinct from existing treatments of serious fungal infections. We will characterise the antifungal capability of P43 and investigate the ways in which it prevents fungal growth. We will further explore its ability to stop growth of other drug resistant fungal pathogens (isolated from patients in South Africa, a hot spot where many drug resistant fungi are emerging) and test its ability to treat invasive fungal infections in preclinical animal models.
This data will provide the key initial characterisation of this potential therapy, enabling follow-on clinical assessment of P43 potential as a new class(es) of antifungal drugs to combat global AFR.