Zooming into the most recent evolution of yeast pathogens

Infections caused by fungi pose a serious health threat, affecting 1,000 million people and causing 1.5 million deaths each year worldwide. The problem has been growing over the last decades as more people received medical treatments that predispose towards such infections. From a clinical perspective, treating fungal infections is difficult because available antifungal drugs are expensive and have undesired side effects. In addition, the incidence of drug-resistant strains is on the rise, which often leads to therapeutic failure. Thus, there is a need to improve current treatments for fungal infections. A promising strategy to achieve this is to study how these pathogens have adapted, from an evolutionary (genomic) perspective, to the human host and to antifungal drugs. This may help us understand the molecular mechanisms of virulence and drug resistance, leading to better therapies in the future. In this work we addressed this issue for Candida pathogens, a group of yeasts that are the primary cause of hospital-acquired fungal infections. We figured out that the growing amount of genome sequences deposited in public databases provided a unique opportunity to ‘zoom in’ and study the most recent steps of this evolutionary process, happening between strains of a given species. We analysed ~2,000 public genomes from clinical isolates of six major Candida pathogens sampled around the world. On the one hand, we explored the genes with signs of recent selection in our genomic datasets, which inform about biological processes underlying adaptation to human-related environments. On the other hand, we used our dataset to find genetic variants underlying drug resistance. Our results highlight that adaptation to humans is species-dependent and multifaceted, affecting different processes such as adhesion and stress response. In addition, we mapped known and new variants that were associated to adaptation to different drugs. Altogether, our work illuminates how these pathogens adapted to humans and to antifungal drugs.