![]() Antifungal resistance in C. glabrata is particularly problematic, as this yeast shows a remarkable ability to adapt to both azoles and echinocandins, thus leading to multidrug resistance (MDR). 6 C. glabrata belongs to the Nakaseomyces clade and is phylogenetically closer to Saccharomyces cerevisiae than to most other Candida pathogens, 7 which may imply different routes for drug adaptation as compared to other Candida species. ![]() 1 C. albicans is the most common cause of candidiasis, but the relative incidence of non-albicans Candida species is on the increase, 6 with C. glabrata often being the second most prevalent cause of infection. 5Ĭandida species are among the main causes of hospital-acquired fungal infections. In this regard, the use of an in vitro evolution approach coupled to whole-genome sequencing represents a promising research avenue. This evolutionary process remains understudied because most of our knowledge derives from already-adapted clones, and from the exploration of a usually limited set of known target genes. 5 Although we know common resistance-conferring mutations and major resistance mechanisms operating in many fungal pathogens, these represent the culmination of an adaptation process. Despite the pressing challenge that the emergence of antifungal resistance represents for human health and food security, we have a limited understanding of the evolutionary processes leading to drug adaptation in fungi. These trends affect all major human fungal pathogenic genera, including Candida, Aspergillus, Cryptococcus, and Pneumocystis. 3, 4 As a result, we are witnessing a global epidemiological change represented by the increased incidence of previously uncommon species with a greater ability to adapt to drugs, the increased failure of therapies due to adaptation of the infecting clone, and the common appearance and rapid spread of deadly outbreaks caused by resistant lineages. The widespread use of antifungal agents to counteract the high clinical, agricultural, and economic burden caused by various fungal pathogens, coupled with the high ability of fungi to adapt to selective pressures, have resulted in an alarming increase in the rates at which fungal species or isolates resistant to one or multiple drugs are identified. 2 Acquisition of antifungal resistance is particularly worrying, given the limited number of available compounds. 1 Current challenges to overcome this trend include the lack of fast and accurate diagnoses and the rise of antifungal drug resistance. Our results shed light on the mutational paths leading to resistance and cross-resistance to antifungal drugs.Įach year, fungal infections affect >1 billion people worldwide and cause 1.5 million deaths. Importantly, we uncover a dual role of ERG3 mutations in resistance to anidulafungin and cross-resistance to fluconazole in a subset of anidulafungin-adapted strains. ![]() Resistance, including multidrug resistance, is often acquired at moderate fitness costs and mediated by mutations in a limited set of genes that are recurrently and specifically mutated in strains adapted to each of the drugs. Our results show widespread ability of rapid adaptation to one or both drugs. Here, we used experimental microevolution to study the adaptation of the yeast pathogen Candida glabrata to fluconazole and anidulafungin, two widely used antifungal drugs with different modes of action. However, the evolutionary processes underpinning the acquisition of antifungal drug resistance are poorly understood. Fungal infections are a growing medical concern, in part due to increased resistance to one or multiple antifungal drugs.
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