Origin of fungal hybrids with pathogenic potential from warm seawater environments

Abstract

Hybridisation is a common event in yeasts often leading to genomic variability and adaptation. The yeast Candida orthopsilosis is a human-associated opportunistic pathogen belonging to the Candida parapsilosis species complex. Most C. orthopsilosis clinical isolates are hybrids resulting from at least four independent crosses between two parental lineages, of which only one has been identified. The rare presence or total absence of parentals amongst clinical isolates is hypothesised to be a consequence of a reduced pathogenicity with respect to their hybrids. Here, we sequence and analyse the genomes of environmental C. orthopsilosis strains isolated from warm marine ecosystems. We find that a majority of environmental isolates are hybrids, phylogenetically closely related to hybrid clinical isolates. Furthermore, we identify the missing parental lineage, thus providing a more complete overview of the genomic evolution of this species. Additionally, we discover phenotypic differences between the two parental lineages, as well as between parents and hybrids, under conditions relevant for pathogenesis. Our results suggest a marine origin of C. orthopsilosis hybrids, with intrinsic pathogenic potential, and pave the way to identify pre-existing environmental adaptations that rendered hybrids more prone than parental lineages to colonise and infect the mammalian host.

Hybrid adaptation is hampered by Haldane’s sieve

“…to not have access to sexual reproduction 116 . Even fungal pathogens evolve through recurrent hybridization events 28,97,[117][118][119][120][121] and acquire antifungal resistance and adapt to new hosts with de novo mutations and LOH [122][123][124][125][126] . It has indeed been shown that to confer full resistance to antifungals, a mutation in a transcriptional regulator needed to be followed by LOH 127 .…”

Long-term stability of acquired drug resistance and resistance associated mutations in the fungal pathogen Nakaseomyces glabratus (Candida glabrata)

“…The second used proxy, rAUC, was defined as area under the log2 drug concentration-vs-AUC, normalized by the maximum AUCMAX where there is no change in growth across all the tested concentrations. For a validation of the agar-based method described here by comparison with a liquid-based method, refer to Del Olmo et al. (2023) and Mixão et al.…”

A yeast love triangle: multiple hybridizations shape genome evolution in thePichia cactophilaspecies complex

“…In such cases, hybrids may survive, and their characteristic genomic plasticity may confer them some advantages, including the ability to survive in new environments (1, 5). Over the last years, a growing number of yeast hybrid lineages have been described (6), and hybridization has been hypothesized as a possible mechanism leading to the emergence of new pathogens, as it is the case of Candida orthopsilosis, Candida metapsilosis, Candida inconspicua, Candida tropicalis or even Candida albicans (1, 7–15).…”