Genome comparisons of Candida glabrata serial clinical isolates reveal patterns of genetic variation in infecting clonal populations

Candida glabrata is an opportunistic fungal pathogen that currently ranks as the second most common cause of candidiasis. Although the mechanisms underlying virulence and drug resistance in C. glabrata are now starting to be elucidated, we still lack a good understanding of how this yeast adapts during the course of an infection. Outstanding questions are whether the observed genomic plasticity of C. glabrata plays a role during infection, or what levels of genetic variation exist within an infecting clonal population. To shed light onto the genomic variation within infecting C. glabrata populations, we compared the genomes of 11 pairs and one trio of serial clinical isolates, each obtained from a single patient. Our results provide a catalog of genetic variations existing within clonal infecting isolates, and reveal an enrichment of non-synonymous changes in genes encoding cell-wall proteins. Genetic variation and the presence of non-synonymous mutations and copy number variations accumulated within the host, suggest that clonal populations entail a non-negligible level of genetic variation that may reflect selection processes that occur within the human body. As we show here, these genomic changes can underlie phenotypic differences in traits that are relevant for infection. TG group acknowledges support from the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership, and grants “Centro de Excelencia Severo Ochoa 2013–2017” SEV-2012-0208, and BFU2015-67107 cofunded by European Regional Development Fund (ERDF), from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857, and grant from the European Union’s Horizon 2020 research and innovation programme under the grant agreement ERC-2016-724173 the Marie Sklodowska-Curie grant agreement No. H2020-MSCA-ITN-2014-642095. This project received support from the INB Grant (PT17/0009/0023 – ISCIII-SGEFI/ERDF).