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Beer, sex and antifungal drugs

Our environment dictates our behaviour. The sheer delight of a child enjoying an ice cream, or an adult eating burnt toast just to survive until coffee time. It’s our sense of taste that drives what we do. Now, this feature pervades throughout life, including fungal pathogens. So, can we use this to our advantage in the fight against disease?

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Mar 27, 2018
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The Review article in Nature Microbiology is here: https://go.nature.com/2pOKjhZ

Fungi make decisions based on the ‘taste’ of their environment through receptors on their surface (much like those on our tongue) called G-protein coupled receptors (GPCRs). Our knowledge of how GPCRs control behaviour stems from the model fungus, yeast, and its regulation of beer and sex. Yeast will ferment when it senses glucose, and will have sex when it senses pheromones. But does the fungal sense of ‘taste’ also define the outcome of disease?  

 Fungi make decisions based on the ‘taste’ of their environment through receptors on their surface (much like those on our tongue) called G-protein coupled receptors (GPCRs). Our knowledge of how GPCRs control behaviour stems from the model fungus, yeast, and its regulation of beer and sex. Yeast will ferment when it senses glucose, and will have sex when it senses pheromones. But does the fungal sense of ‘taste’ also define the outcome of disease? 

Of course it does. The rice blast pathogen Magnaporthe orzyae senses the hydrophobic leaf surface and triggers invasion. Aspergillus species sense nutrients to regulate the production of harmful toxins, which contaminate our food and impede immunity during deadly pulmonary aspergillosis infections. Hence, fungal GPCRs sense the ‘taste’ of their host and promote disease.

Peer pressure influences how we behave and fungi are the same. Again, this involves GPCR-mediated signalling mechanisms. Candida albicans, which causes irritating conditions such as thrush and life-threating candidiasis, senses its own density to control how it grows, influencing disease. But it also ‘tastes’ sugars present in host, or released by a gut microbe, to know when it’s arrived in a hostile environment, enabling it to hide from host immunity. So, Candida communicates with its peers, other microbes and their host, influencing the outcome of disease.

Finally, back to sex, which is more important to fungal diseases than you may imagine. Cryptococcus species, which cause cryptococcosis and cryptococcal meningitis, use GPCRs to sense pheromones to promote sex, providing genetic variation that contributes to the outbreak of hypervirulent diseases. Thus, fungal sex is key to the evolution of disease.

Image 2: GPCRs control fungal traits important for disease.

All these examples show how fungal GPCRs can modulate disease. So, isn’t targeting fungal ‘taste’ receptors a promising strategy to develop new drugs to inhibit a pathogen’s decision to cause disease? And could we impede the evolution of antifungal resistant, or hypervirulent, strains?

But first we must shed more light on the structure and function of these poorly understood receptors and the stimuli they detect.

Here, we set out a frame work for how this may be achieved. Let’s do it.

By Neil A. Brown and Gustavo H. Goldman

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Neil Brown

BBSRC Fellow and Lecturer, University of Bath

I am an early career molecular fungal biologist and BBSRC Future Leader Fellow / Lecturer at the University of Bath. I am motivated to discover new ways to fight major fungal diseases that threaten our food security and health. I focus on the cereal pathogen Fusarium graminearum and the food spoilage mould Aspergillus nidulans, which produce harmful toxins that can contaminate our food. A fungal pathogen landing on a plant must decide if it is suitable, where to infect, and when to deploy different virulence strategies. The goal of my research is to discover how fungal pathogens sense the ‘taste’ of their host environment, to coordinate disease and toxin production.

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