Active Infection & Immunity Plants, Animals & Ecology

Transporter repertoire evolution in the Fungi: adaptation to vertebrate- derived niches

In plain English

AI plain-English summary

Fungi use surface proteins called transporters to suck in nutrients from their surroundings, and this project will map how those transporters evolved as certain fungi became capable of infecting vertebrates. The problem is that fungal pathogens are a growing threat to human health, yet scientists have only a patchy understanding of what allows a harmless soil fungus to turn into a pathogen. The key may lie in the transporters: a fungus can only colonise an environment—including a human lung or bloodstream—if its surface carries the right set of proteins to capture available nutrients. This project will systematically compare transporter repertoires across the entire fungal family tree, pinpointing which changes correlate with the emergence of vertebrate-infecting species. The team will then test those candidate transporters in lab-grown cells to confirm what nutrients they actually take up. This is fundamental science. It will not produce a drug or diagnostic tomorrow. But by revealing the metabolic weak spots unique to pathogenic fungi—the specific nutrients they must scavenge to survive inside a host—it could eventually point toward new antifungal targets. It may also help predict which harmless fungi carry the evolutionary potential to become future human pathogens.

View original technical description
The Fungi are a highly diverse kingdom unified by one evolutionary trend; osmotrophy. Osmotrophy involves the external digestion of target compounds and the subsequent uptake of liberated metabolites into the cell. As such, how fungi adapt to their environment is determined by the repertoire of metabolite transporter proteins localised to the surface membrane. These features determine which environments a fungus can colonise and how they compete with others. Previous work has suggested that adaptation to pathogenic life-styles is underpinned by changes in transporter protein repertoire. The aim of this project is to identify how transporter repertoire has changed across the fungal tree of life, identify changes that correlate with the rise of pathogenic clades - particularly vertebrate pathogenic clades - and then use heterologous protein expression in model systems to characterise the substrate transportation function of the transporters identified. This work will enable us to understand how fungal transporter protein evolution relates to adaptation to vertebrate pathogenic niche on a kingdom-level scale and will allow us to identify how changes in metabolite-uptake underpin pathogen emergence. These data will provide the basic science for targeting metabolic adaptations unique to vertebrate pathogens as therapeutic targets and identify trends that will underpin future pathogen emergence.

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Researchers

David Milner (EPMC Awardee)Thomas Richards (EPMC Awardee)

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Original classification

Biology of Fungal Adaptation

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