Antimicrobial resistance in fungi

Research in Edinburgh is addressing the impact of fungal resistance to antibiotics in human, veterinary and environmental health.

Antimicrobial resistance in fungi is an often overlooked aspect of AMR, but is an increasing problem in One Health.  Alongside a rise in azole resistance in agricultural fungal pathogens, there is an increase in patients presenting with clinical fungal infections that are also resistant to antmicrobials. 

Work in several research groups in Edinburgh is studying a number of different fungal pathogens, to understand how resistance arises, and what implications this has for use and development of antifungal drugs.

Online fungal AMR workshop

Edinburgh’s broad interest in fungal research was discussed at an online meeting on 26 November 2020.

The meeting welcomed guest speaker from the FungiSphere a research node within the Marie Bashir Institute for Infectious Diseases and Biosecurity at the University of Sydney. Dr Justin Beardsley, coordinator of FungiShpere, showcased how this new cross disciplinary research initiative had increased the quality and quantity of research applications through collaborations around One Health and AMR. 

Attendees then heard from five other research groups across the University - see details below.

FungiSphere, University of Sydney

About our research

Robin Allshire, School of Biological Sciences – Epigenetic Regulation of Anti-fungal Resistance

The Allshire lab uses fission yeast, Schizosaccharomyces pompe, to study the process of heterochromatin silencing and how this is may influence the epigenetic factors implicated in the development of antifungal resistance.

Robin is interested in whether epigenetic heterochromatin mutants are linked to common pathways of drug resistance (e.g. it is thought that azole-based fungicides used on crops target same pathways as human anti-fungals).

Can we use our knowledge of epigenetic regulation to intervene and reduce resistance to anti-fungals in the future?

Allshire lab website

Kevin Hardwick, School of Biological Sciences – Cryprtococcus neoformans infection

The Hardwick lab is interested in the process of Cryptococcus infection and the role of polyploidy in a stage of fungal cell development (so-called Titan cells) in the lung.

They are using flow cytometry to monitor ploidy transitions (i.e. making daughter cells) and the influence of cell cycle checkpoint inhibitors such as spindle checkpoint kinases.

They are interested in whether these kinase inhibitors, in combination with anti-microtubule inhibitors, might make an effective combination treatment for this deadly infection.

Hardwick lab website

Vasso Makrantoni, Infection Medicine – Fungal genome instability and disease

Genetic plasticity in the human fungal pathogen, C. albicans is instrumental to drive adaptation to the host environment.

Chromosome instability driven by Candida-specific cohesin’s regulation could be one of the means to achieve this genetic plasticity.

Vasso is interested in addressing how cohesin is loaded, maintained and dissolved in this fungus when challenged under different environmental stresses.  SHe is starting her own lab, with the ultimate goal is that novel insights into the mechanisms controlling the function of cohesins in C. albicans could guide the development of specific antifungal drugs.

Edward Wallace, School of Biological Sciences – Fungal adaptive responses regulated by mRNA

The Wallce lab is interested in the role of messenger RNA in how cells adapt to their environment.

They are studying how a fungal virulence factor (Ssd1) controls translation of mRNAs affecting cell wall growth in fungi, and are interested in how similar translation regulatory factors help to build the cell wall and contribute to antifungal responses. 

Edward is an expert in ribosome profiling for the high-throughput study of translation, for example identifying a large number of alternative translation events in Cryptococcus that may generate alternative protein isoforms. To study these processes in mechanistic detail, the Wallace lab are building a synthetic biology / reporter gene toolkit for Cryptococcus.

Wallace lab website

Mutapi lab (Lorraine Pfavayi), School of Biological Sciences – Burden of Fungal Diseases in Zimbabwe

Lorraine Pfavayi, a PhD student in Francisca Mutapi's lab is interested in the incidence and prevalence of fungal infections in Zimbabwe.

There is a wide spectrum of fungal diseases from those causing superficial skin infections to more chronic fungal diseases. Lorraine is gathering data from a wide range of sources to quantify the burden as well as raise awareness of these fungal infections which are often under reported.

Mutapi lab website