Biology subjects

Horianopoulos, L. C.

Publications and source records attributed to Horianopoulos, L. C..

3 recordsLinked to original sources

bioRxiv2025

A trait syndrome ties cell morphology to glycolysis across the yeast subphylum

Traits that co-vary across species can provide fundamental insights into the trade-offs and constraints that govern their evolution. It was recently reported that glucose uptake rates (GUR) are inversely correlated with the cell surface area-to-volume (SA:V) ratio across 11 yeast species. Here we substantially expand this analysis to 282 species to test whether the GUR-SA:V correlation generalizes across the ancient Saccharomycotina yeast subphylum and to determine the contribution of shared evolutionary history to the co-variation of these two traits. Using regression models that account for co-variation due to phylogeny, we found that extracellular acidification rates (ECAR, which we used as a scalable proxy for GUR) had a weak, but significant, correlation with SA:V across Saccharomycotina. We found additional weak, but significant, correlations between ECAR with genome sizes and growth rates. Our findings largely agree with the recently reported correlations between GUR and SA:V ratio, but they also show that there are likely several other associated variables, including genome size. Specifically, yeasts that consume glucose faster tend to have lower SA:V, faster growth rates, and larger genomes. Our results suggest that a trait syndrome governs several metabolic, genomic, and morphological traits across the yeast subphylum.

evolutionary biology↗

bioRxiv2024

Machine learning uncovers gene families impacting oxidative stress resistance across yeasts

Reactive oxygen species (ROS) are highly reactive molecules encountered by yeasts during routine metabolism and during interactions with other organisms, including host infection. Here, we characterized the variation in resistance to ROS across the ancient yeast subphylum Saccharomycotina and used machine learning (ML) to identify gene families whose sizes were predictive of ROS resistance. The most predictive features were enriched in gene families related to cell wall organization and included two reductase gene families. We estimated the quantitative contributions of features to each species classification to guide experimental validation and showed that overexpression of the old yellow enzyme (OYE) reductase increased ROS resistance in Kluyveromyces lactis, while Saccharomyces cerevisiae mutants lacking multiple mannosyltransferase-encoding genes were hypersensitive to ROS. Altogether, this work provides a framework for how ML can uncover genetic mechanisms underlying trait variation across diverse species and inform trait manipulation for clinical and biotechnological applications.

microbiology↗

bioRxiv2024

Glutathione metabolism impacts fungal virulence by modulating the redox environment

Pathogens must overcome the hostile conditions of their hosts to survive, proliferate and cause disease. The fungal pathogen Cryptococcus neoformans is particularly adept at mitigating challenges in the host environment and has developed an arsenal of defense mechanisms to evade oxidative and nitrosative agents released by phagocytic cells during infection. Among these mechanisms, melanin production is crucially linked to both fungal virulence and defense against harmful free radicals that facilitate host innate immunity and clearance of invading pathogens. Here, we employed comparative global metabolomics to demonstrate that metabolism of the antioxidant glutathione (GSH) is inextricably linked to redox-active processes that facilitate melanin production, and that genetic perturbations in GSH biosynthesis affect fungal growth and virulence in a murine model of cryptococcosis. Furthermore, we show that disruption of GSH biosynthesis leads to overaccumulation of reducing and acidic compounds in the extracellular environment of mutant cells. These changes not only impacted melanin formation but also influenced titan cell and urease production as well as survival in macrophages. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.

microbiology↗