Overview

MetaFungal (Metabolism of carboxylic acids in Fungal Infections) - PTDC/BIA-MIC/5246/2020 (https://doi.org/10.54499/PTDC/BIA-MIC/5246/2020) - is a project funded by national funds through the ‘Fundação para a Ciência e a Tecnologia’ (FCT) I.P.

MetaFungal integrates state-of-the-art approaches in pathogenomics, molecular biology, infection biology and bioimaging, to investigate how nutrient utilization, particularly of carboxylic acids, influences fungal adaptation and pathogenic potential. By combining studies in Candida albicans with comparative analyses in Saccharomyces cerevisiae, the project explores how transporter families and metabolic regulation shape both environmental adaptation and virulence.

Several studies in Candida have consistently demonstrated that carboxylate transporters are
strongly upregulated following phagocytosis, reinforcing the idea that carboxylate assimilation, dependent on plasma membrane (PM) transporters, is an integral part of the response to phagocytosis.

In yeast two families of PM transport proteins mediate the uptake of carboxylates:

Jen transporters, belonging to the sialate:H+ symporter (SHS) family
Ato proteins (acetate transporter ortholog), assigned to the acetate uptake transporter (AceTr) family.

This project focuses on understanding the function of these transporters in both C. albicans and S. cerevisiae.

In C. albicans, 8 Ato-like proteins have been identified, but their physiological roles remain unclear. We aim to investigate these proteins, particularly in the context of fungal infections, to
uncover their contributions to nutrient acquisition and pathogenicity.

Our studies also include the known carboxylate transporters in C. albicans (CaJen1 and CaJen2) and their homologues in S. cerevisiae (Jen1, Ato1, Ato2, and Ato3). Comparative analyses between these species enable more effective testing of scientific hypotheses, particularly given that S. cerevisiae possesses only three Ato family members and a single Jen transporter.

Importantly, our preliminary findings suggest a potential interplay between Jen and Ato transporters, opening new perspectives on how these systems coordinate to support fungal metabolism and virulence.

Our impact

MetaFungal project is dedicated to advancing knowledge in fungal research to improve global health and environment.

Considering the different niches in which Candida grows in the body, the results of our project have the potential to fundamentally advance our understanding on the interactions between these pathogens and the human host. Using novel metabolic and molecular-based approaches, we ultimately expect to identify novel points of fragility in C. albicans that can be developed, in the future, as therapeutic targets to treat Candida infections.

Common sites of the host for C. albicans infections

Objectives

To combine interdisciplinary and cutting-edge approaches to address fundamental questions about how yeast cells control the transport and sense the presence of carboxylic
acids