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Impact of inter-species hybridisation on antifungal drug response in the Saccharomyces genus
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Impact of inter-species hybridisation on antifungal drug response in the Saccharomyces genus
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Journal Article
Impact of inter-species hybridisation on antifungal drug response in the Saccharomyces genus
2024
Overview
Background
Antifungal drug resistance presents one of the major concerns for global public health, and hybridization allows the development of high fitness organisms that can better survive in restrictive conditions or in presence of antifungal agents. Hence, understanding how allelic variation can influence antifungal susceptibility in hybrid organisms is important for the development of targeted treatments. Here, we exploited recent advances in multigenerational breeding of
hemiascomycete
hybrids to study the impact of hybridisation on antifungal resistance and identify quantitative trait loci responsible for the phenotype.
Results
The offspring of
Saccharomyces cerevisiae
x
S. kudriavzevii
hybrids were screened in the presence of six antifungal drugs and revealed a broad phenotypic diversity across the progeny. QTL analysis was carried out comparing alleles between pools of high and low fitness offspring, identifying hybrid-specific genetic regions involved in resistance to fluconazole, micafungin and flucytosine. We found both drug specific and pleiotropic regions, including 41 blocks containing genes not previously associated with resistance phenotypes. We identified linked genes that influence the same trait, namely a hybrid specific ‘super’ QTL, and validated, via reciprocal hemizygosity analysis, two causal genes,
BCK2
and
DNF1
. The co-location of genes with similar phenotypic impact supports the notion of an adaption process that limits the segregation of advantageous alleles via recombination.
Conclusions
This study demonstrates the value of QTL studies to elucidate the hybrid-specific mechanisms of antifungal susceptibility. We also show that an inter-species hybrid model system in the
Saccharomyces
background, can help to decipher the trajectory of antifungal drug resistance in pathogenic hybrid lineages.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Alleles
/ Animal Genetics and Genomics
/ Antifungal Agents - pharmacology
/ Biomedical and Life Sciences
/ Breeding
/ COVID-19
/ Drug resistance in microorganisms
/ Drug Resistance, Fungal - genetics
/ Fungi
/ Genes
/ Genomes
/ HIV
/ Human immunodeficiency virus
/ Hybrids
/ Microbial Genetics and Genomics
/ Mutation
/ Saccharomyces - drug effects
/ Testing
/ Yeast
