Understanding Drug Resistance in Human Fungal Pathogens

The emergence of drug-resistant pathogens is an increasing problem as it
diminishes our ability to treat common infections. Especially alarming is the
global spread of antifungal drug resistance occurring when fungal pathogens
no longer respond to drugs.
Fungal pathogens are a threat to animal, plant and ecosystem health.
Indeed, fungal diseases cause ~ 1.5 million human death annually.
Pathogenic fungi are also a worldwide threat to food security, as they can
infect plants and crops, and fungal infections are driving the extinction of
South Coast Biosciences Doctoral Training Partnership (SoCoBio DTP)
Email: socobio@soton.ac.uk Website: www.southcoastbiosciencesdtp
several animal groups, including bats, amphibians and reptiles.
This project aims to understand the mechanisms of antifungal drug
resistance in Candida albicans, the most common human fungal pathogen.
C. albicans commonly live in the human body without causing any harm.
However, C. albicans can cause life-threatening infections in
immunocompromised individuals such as cancer patients undergoing
chemotherapy treatments. There are only three types of effective antifungal
drugs to treat C. albicans infection, and the emergence of drug resistance
severely hinders our therapeutic options.
Proteins are the primary functional molecules in all living organisms,
including fungal pathogens. Proteins can be chemically modified in a process
known as Post-Translation Modification (PTM). PTMs modulate the
function, localisation and activity of proteins.
The Buscaino lab has recently identified SUMOylation as a key PTM
regulating C. albicans antifungal drug resistance. Indeed, C. albicans strains
lacking key SUMO enzymes develop resistance to antifungal drugs by
accumulating specific genomic rearrangements. This PhD project combines
our expertise in fungal genetics, genomics (Buscaino), quantitative
proteomics and bioinformatics (Giamas) to unveil how and why C. albicans
protein SUMOylation leads to drug resistance and how the SUMOylation
machinery regulates the C. albicans proteome in response to antifungal
drugs.