Tetraploidy accelerates adaption under drug-selection in a fungal pathogen

Avramovska, Ognenka; Rego, Emily; Hickman, Meleah A.

doi:10.1101/2021.02.28.433243

“…A second evolution experiment done at the same subinhibitory level of FLC, however, did find ∼30% of replicates had increased resistance ( Todd and Selmecki 2020 ). Another evolution experiment that paired a strong selective pressure with a long period of time between transfers (7 days) in caspofungin (a different class of drug), also found that many evolved diploid lines did not increase in resistance by the end of the 59-day experiment ( Avramovska et al 2021 ). In contrast, increased FLC resistance was evident in the earliest C. albicans evolution experiments, conducted in the T101 background in continually increasing levels of FLC for ∼330 generations ( Cowen et al 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Acquisition of cross-azole tolerance and aneuploidy in Candida albicans strains evolved to posaconazole

Kukurudz

¹

,

Chapel

²

,

Wonitowy

³

et al. 2022

View full text Add to dashboard Cite

A number of in vitro studies have examined the acquisition of drug resistance to the triazole fluconazole, a first-line treatment for many Candida infections. Much less is known about posaconazole, a newer triazole. We conducted the first in vitro experimental evolution of replicates from eight diverse strains of C. albicans in a high level of the fungistatic drug posaconazole. Approximately half of the 132 evolved replicates survived 50 generations of evolution, biased towards some of the strain backgrounds. We found that although increases in drug resistance were rare, increases in drug tolerance (the slow growth of a subpopulation of cells in a level of drug above the resistance level) were common across strains. We also found that adaptation to posaconazole resulted in widespread cross-tolerance to other azole drugs. Widespread aneuploidy variation was also observed in evolved replicates from some strain backgrounds. Trisomy of chromosomes 3, 6, and R was identified in 11 of 12 whole-genome sequenced evolved SC5314 replicates. These findings document rampant evolved cross-tolerance among triazoles and highlight that increases in drug tolerance can evolve independently of drug resistance in a diversity of C. albicans strain backgrounds.

show abstract

“…Consistent with these results in POS, very few replicates evolved to a subinhibitory level of FLC increased in FLC resistance (Gerstein and Berman 2020), though a second evolution experiment done at the same sub-inhibitory level of FLC found ∼30% of replicates had increased resistance (Todd and Selmecki 2020). An evolution experiment that similarly paired a strong selective pressure with a long period of time (7 days) between transfers to caspofungin, a different drug class, also found that many evolved diploid lines did not increase in resistance by the end of the 59-day experiment (Avramovska et al . 2021).…”

Section: Discussionmentioning

confidence: 99%

Acquisition of cross-azole tolerance and aneuploidy inCandida albicansstrains evolved to posaconazole

Kukurudz

¹

,

Chapel

²

,

Wonitowy

³

et al. 2022

Preprint

View full text Add to dashboard Cite

A number of in vitro studies have examined the acquisition of drug resistance to the triazole fluconazole, a first-line treatment for many Candida infections. Much less is known about posaconazole, a newer triazole. We conducted the first in vitro experimental evolution of replicates from eight diverse strains of C. albicans in a high level of the fungistatic drug posaconazole. Approximately half of the 132 evolved replicates survived 50 generations of evolution, biased towards some of the strain backgrounds. We found that although increases in drug resistance were rare, increases in drug tolerance (the slow growth of a subpopulation of cells in a level of drug above the resistance level) were common across strains. We also found that adaptation to posaconazole resulted in widespread cross-tolerance to other azole drugs. Widespread aneuploidy variation was also observed in evolved replicates from some strain backgrounds. Trisomy of chromosomes 3, 6, and R was identified in 11 of 12 whole-genome sequenced evolved SC5314 replicates. These findings document rampant evolved cross-tolerance among triazoles and highlight that increases in drug tolerance can evolve independently of drug resistance in a diversity of C. albicans strain backgrounds.

show abstract

“…It is easy to see that both α and β concur in defining line (4). This is what originates the conditional nature of the ECM algorithm, i.e.…”

Section: Supplementary Materialsmentioning

confidence: 93%

“…Ploidy variation can be associated with a response or adaptation to environmental factors (13), and it is a phenomenon commonly detected in cancer cells (14) and several pathogenic fungi (i.e. Cryptococcus neoformans , Candida albicans and Candida glabrata ) and monocellular parasites (46; 35; 16; 54; 53; 19; 4).…”

Section: Introductionmentioning

confidence: 99%

HMMploidy: inference of ploidy levels from short-read sequencing data

Soraggi

¹

,

Rhodes

²

,

Altinkaya

³

et al. 2021

Preprint

View full text Add to dashboard Cite

The inference of ploidy levels from genomic data is important to understand molecular mechanisms underpinning genome evolution. However, current methods based on allele frequency and sequencing depth variation do not have power to infer ploidy levels at low- and mid-depth sequencing data, as they do not account for data uncertainty. Here we introduce HMMploidy, a novel tool that leverages the information from multiple samples and combines the information from sequencing depth and genotype likelihoods. We demonstrate that HMMploidy outperforms existing methods in most tested scenarios, especially at low-depth with large sample size. HMMploidy further allows for local inferences of ploidy change to detect within-chromosome variations. We apply HMMploidy to sequencing data from the pathogenic fungus Cryptococcus neoformans and retrieve pervasive patterns of polyploidy and aneuploidy, even when artificially downsampling the sequencing data. We envisage that HMMploidy will have wide applicability to low-depth sequencing data from polyploid and aneuploid species.

show abstract

Tetraploidy accelerates adaption under drug-selection in a fungal pathogen

Cited by 6 publications

References 61 publications

Acquisition of cross-azole tolerance and aneuploidy in Candida albicans strains evolved to posaconazole

Acquisition of cross-azole tolerance and aneuploidy in Candida albicans strains evolved to posaconazole

Acquisition of cross-azole tolerance and aneuploidy inCandida albicansstrains evolved to posaconazole

HMMploidy: inference of ploidy levels from short-read sequencing data

Contact Info

Product

Resources

About