Ploidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution

Todd, Robert T.; Forche, Anja; Selmecki, Anna

doi:10.1128/microbiolspec.funk-0051-2016

Cited by 76 publications

(63 citation statements)

References 173 publications

(240 reference statements)

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“…Ploidy change is a common occurrence in eukaryotic cells being integral to sexual reproduction, tumorigenesis, and the development of certain somatic tissues (Storchova & Pellman, 2004;Bennett et al, 2014;Todd et al, 2017). A striking example of ploidy change occurs in C. albicans where diploid cells mate to form tetraploid cells that then reduce their ploidy via aberrant mitotic divisions (Bennett & Johnson, 2003;Forche et al, 2008;Bennett, 2015).…”

Section: Discussionmentioning

confidence: 99%

Metabolism‐induced oxidative stress and DNA damage selectively trigger genome instability in polyploid fungal cells

et al. 2019

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Understanding how cellular activities impact genome stability is critical to multiple biological processes including tumorigenesis and reproductive biology. The fungal pathogen Candida albicans displays striking genome dynamics during its parasexual cycle as tetraploid cells, but not diploid cells, exhibit genome instability and reduce their ploidy when grown on a glucose‐rich “pre‐sporulation” medium. Here, we reveal that C. albicans tetraploid cells are metabolically hyperactive on this medium with higher rates of fermentation and oxidative respiration relative to diploid cells. This heightened metabolism results in elevated levels of reactive oxygen species (ROS), activation of the ROS‐responsive transcription factor Cap1, and the formation of DNA double‐strand breaks. Genetic or chemical suppression of ROS levels suppresses each of these phenotypes and also protects against genome instability. These studies reveal how endogenous metabolic processes can generate sufficient ROS to trigger genome instability in polyploid C. albicans cells. We also discuss potential parallels with metabolism‐induced instability in cancer cells and speculate that ROS‐induced DNA damage could have facilitated ploidy cycling prior to a conventional meiosis in eukaryotes.

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Section: Discussionmentioning

confidence: 99%

Metabolism‐induced oxidative stress and DNA damage selectively trigger genome instability in polyploid fungal cells

et al. 2019

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“…Failures in kinetochore assembly and attachment increase the probability of chromosome mis-segregation leading to aneuploidy [61]. While these drastic genome changes can be detrimental to the organism, formation of aneuploidy and polyploidy is an important strategy orchestrated by pathogens to adapt to the environment during periods of stress [62]. Polyploidy and aneuploidy are prevalent in Phytophthora natural isolates and in progeny from sexual reproduction [36,[63][64][65][66].…”

Section: Plos Geneticsmentioning

confidence: 99%

Long transposon-rich centromeres in an oomycete reveal divergence of centromere features in Stramenopila-Alveolata-Rhizaria lineages

et al. 2020

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Centromeres are chromosomal regions that serve as platforms for kinetochore assembly and spindle attachments, ensuring accurate chromosome segregation during cell division. Despite functional conservation, centromere DNA sequences are diverse and often repetitive, making them challenging to assemble and identify. Here, we describe centromeres in an oomycete Phytophthora sojae by combining long-read sequencing-based genome assembly and chromatin immunoprecipitation for the centromeric histone CENP-A followed by high-throughput sequencing (ChIP-seq). P. sojae centromeres cluster at a single focus at different life stages and during nuclear division. We report an improved genome assembly of the P. sojae reference strain, which enabled identification of 15 enriched CENP-A binding regions as putative centromeres. By focusing on a subset of these regions, we demonstrate that centromeres in P. sojae are regional, spanning 211 to 356 kb. Most of these regions are transposon-rich, poorly transcribed, and lack the histone modification H3K4me2 but are embedded within regions with the heterochromatin marks H3K9me3 and H3K27me3. Strikingly, we discovered a Copia-like transposon (CoLT) that is highly enriched in the CENP-A chromatin. Similar clustered elements are also found in oomycete relatives of P. sojae, and may be applied as a criterion for prediction of oomycete centromeres. This work reveals a divergence of centromere features in oomycetes as compared to other organisms in the Stramenopila-Alveolata-Rhizaria (SAR) supergroup including diatoms and Plasmodium falciparum that have relatively short and simple regional centromeres. Identification of P. sojae centromeres in turn also advances the genome assembly.

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“…Previously, PP has been demonstrated to strongly inhibit the growth of the fluconazole-resistant i(5L) strain of C. albicans, which contains double copies of the left arm of chromosome 5 (Selmecki et al, 2006;Chen et al, 2015), and enhances the antifungal efficacy of fluconazole, demonstrating the efficacy of PP toward aneuploidy-based azole resistance. Acquisition of aneuploidy has been documented in pathogenic fungi C. albicans, Saccharomyces cerevisiae, and Cryptococcus neoformans (Todd et al, 2017). Specific environmental conditions, such as antifungal stress and fungal interactions with the host, might result in aneuploidy, which has been associated with drug resistance of fungi (Todd et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Pyrvinium Pamoate and Azoles Against Aspergillus fumigatus in vitro and in vivo

et al. 2020

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The effects of pyrvinium pamoate alone and in combination with azoles [itraconazole (ITC), posaconazole (POS), and voriconazole (VRC)] were evaluated against Aspergillus fumigatus both in vitro and in vivo. A total of 18 clinical strains of A. fumigatus were studied, including azole-resistant isolates harboring the combination of punctual mutation and a tandem repeat sequence in the Cyp51A gene (AFR1 with TR34/L98H and AFR2 with TR46/Y121F/T289A). The in vitro results revealed that pyrvinium individually exhibited minimal inhibitory concentration (MIC) of 2 µg/ml against AFR1 but was ineffective against other tested strains (MIC > 32 µg/ml). Nevertheless, the synergistic effects of pyrvinium with ITC, VRC, or POS were observed in 15 [83.3%, fractional inhibitory concentration index (FICI) 0.125-0.375], 11 (61.1%, FICI 0.258-0.281), and 16 (88.9%, FICI 0.039-0.281) strains, respectively, demonstrating the potential of pyrvinium in reversion of ITC and POS resistance of both AFR1 (FICI 0.275, 0.281) and AFR2 (FICI 0.125, 0.039). The effective MIC ranges in synergistic combinations were 0.25-8 µg/ml for pyrvinium, 0.125-4 µg/ml for ITC, and 0.125 µg/ml for both VRC and POS, demonstrating 4-to 32-fold reduction in MICs of azoles and up to 64-fold reduction in MICs of pyrvinium, respectively. There was no antagonism. The effect of pyrvinium-azole combinations in vivo was evaluated by survival assay and fungal burden determination in the Galleria mellonella model infected with AF293, AFR1, and AFR2. Pyrvinium alone significantly prolonged the survival of larvae infected with AF293 (P < 0.01) and AFR1 (P < 0.0001) and significantly decreased the tissue fungal burden of larvae infected with AFR1 (P < 0.0001). Pyrvinium combined with azoles significantly improved larvae survival (P < 0.0001) and decreased larvae tissue fungal burden in all three isolates (P < 0.0001). Notably, despite AFR2 infection was resistant to VRC or pyrvinium alone, pyrvinium combined with VRC significantly prolonged survival of both AFR1 and AFR2 infected larvae (P < 0.0001). In summary, the preliminary results indicated that the combination with pyrvinium and azoles had the potential to overcome azole resistance issues of A. fumigatus and could be a promising option for anti-Aspergillus treatment.

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Ploidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution

Cited by 76 publications

References 173 publications

Metabolism‐induced oxidative stress and DNA damage selectively trigger genome instability in polyploid fungal cells

Metabolism‐induced oxidative stress and DNA damage selectively trigger genome instability in polyploid fungal cells

Long transposon-rich centromeres in an oomycete reveal divergence of centromere features in Stramenopila-Alveolata-Rhizaria lineages

Synergistic Effect of Pyrvinium Pamoate and Azoles Against Aspergillus fumigatus in vitro and in vivo

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