Mitotic Recombination Accelerates Adaptation in the Fungus Aspergillus nidulans

Schoustra, Sijmen E.; Debets, A.J.M.; Slakhorst, M.; Hoekstra, Rolf F.

doi:10.1371/journal.pgen.0030068

Cited by 113 publications

(75 citation statements)

References 26 publications

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“…This genomic convergence is independent of mating or meiosis and may occur by chromosome nondisjunction during mitosis (e.g., to drive a ploidy reduction) or by endoreduplication (e.g., to drive a ploidy increase). Aspergillus nidulans, a primarily haploid ascomycete, also undergoes a reduction in ploidy (from diploid to haploid) via a parasexual mechanism when grown continuously in standard medium (48). It is therefore apparent that extended culture can induce ploidy changes in diverse fungal species although the precise molecular mechanisms driving parasexual ploidy changes remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Parasexuality and Ploidy Change in Candida tropicalis

et al. 2013

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Candida species exhibit a variety of ploidy states and modes of sexual reproduction. Most species possess the requisite genes for sexual reproduction, recombination, and meiosis, yet only a few have been reported to undergo a complete sexual cycle including mating and sporulation. Candida albicans, the most studied Candida species and a prevalent human fungal pathogen, completes its sexual cycle via a parasexual process of concerted chromosome loss rather than a conventional meiosis. In this study, we examine ploidy changes in Candida tropicalis, a closely related species to C. albicans that was recently revealed to undergo sexual mating. C. tropicalis diploid cells mate to form tetraploid cells, and we show that these can be induced to undergo chromosome loss to regenerate diploid forms by growth on sorbose medium. The diploid products are themselves mating competent, thereby establishing a parasexual cycle in this species for the first time. Extended incubation (>120 generations) of C. tropicalis tetraploid cells under rich culture conditions also resulted in instability of the tetraploid form and a gradual reduction in ploidy back to the diploid state. The fitness levels of C. tropicalis diploid and tetraploid cells were compared, and diploid cells exhibited increased fitness relative to tetraploid cells in vitro, despite diploid and tetraploid cells having similar doubling times. Collectively, these experiments demonstrate distinct pathways by which a parasexual cycle can occur in C. tropicalis and indicate that nonmeiotic mechanisms drive ploidy changes in this prevalent human pathogen.

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Section: Discussionmentioning

confidence: 99%

Parasexuality and Ploidy Change in Candida tropicalis

et al. 2013

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“…Sexual reproduction can lead to a high degree of genetic variability and a limited amount of clonality, as has occurred globally in populations of the wheat pathogens Mycosphaerella graminicola and Phaeosphaeria nodorum (Chen and McDonald, 1996;Stukenbrock et al, 2006). The occurrence of parasexual cycles may also generate variation in an asexual population (Schoustra et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Virulence and genetic diversity among isolates of Mycosphaerella fijiensis in two regions of Brazil

Silva

Santos

Sousa³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Black sigatoka, caused by the fungus Mycosphaerella fijiensis (anamorphic stage: Paracercospora fijiensis), was first detected in Brazil in early 1998 in the Benjamin Constant and Tabatinga municipalities in the State of Amazonas, near to where the borders of Brazil, Colombia, and Peru converge. Understanding how cultivars react to the pathogen, and characterizing the genetic variability of isolates from two distant and distinct banana-producing regions, are important for determining the virulence of M. fijiensis. In the present study, the genetic diversity of 22 M. fijiensis isolates was assessed using simple sequence repeats (SSR) markers, and their virulence was determined following inoculation on three different banana tree cultivars. All 22 isolates caused symptoms of the disease in the Maçã and Prata Comum cultivars 45 days after inoculation, and at least two virulence groups were identified for the Maçã and Prata Comum cultivars. For the D'Angola cultivars, two virulence groups were observed only after 60 days post-inoculation, and three of the isolates were not virulent. Using SSR markers, the isolates from two different regions of Brazil were placed into two genetic groups, both genetically distant from the Mf 138 isolate collected in Leticia, Colombia. There was no evidence of correlation between the virulence groups and the genetic diversity groups. These results demonstrate variability in virulence between isolates as measured by the severity of black sigatoka in the analyzed cultivars.

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“…1A). Schoustra et al (15) proposed that mitotic recombination has the potential to accelerate adaptation rates in A. nidulans. We suggest that the presence of large numbers of Hülle cells could be a sign that the colony has become potentiated for cell fusion.…”

Section: Discussionmentioning

confidence: 99%

“…Especially for echinocandins, clinically resistant strains were isolated shortly after their launch (11,12). The strong adaptation ability of fungi is well documented (13)(14)(15)(16), so it was not surprising to see antifungal drug resistance emerging quickly. Mutation hot spots in FKS1, which encodes beta-glucan synthase, were detected in some of the resistant strains but not in all (10)(11)(12).…”

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confidence: 99%

Using Aspergillus nidulans To Identify Antifungal Drug Resistance Mutations

Kaminskyj

2014

Eukaryot Cell

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Systemic fungal infections contribute to at least 10% of deaths in hospital settings. Most antifungal drugs target ergosterol (polyenes) or its biosynthetic pathway (azoles and allylamines), or beta-glucan synthesis (echinocandins). Antifungal drugs that target proteins are prone to the emergence of resistant strains. Identification of genes whose mutations lead to targeted resistance can provide new information on those pathways. We used Aspergillus nidulans as a model system to exploit its tractable sexual cycle and calcofluor white as a model antifungal agent to cross-reference our results with other studies. Within 2 weeks from inoculation on sublethal doses of calcofluor white, we isolated 24 A. nidulans adaptive strains from sectoring colonies. Meiotic analysis showed that these strains had single-gene mutations. In each case, the resistance was specific to calcofluor white, since there was no cross-resistance to caspofungin (echinocandin). Mutation sites were identified in two mutants by next-generation sequencing. These were confirmed by reengineering the mutation in a wild-type strain using a gene replacement strategy. One of these mutated genes was related to cell wall synthesis, and the other one was related to drug metabolism. Our strategy has wide application for many fungal species, for antifungal compounds used in agriculture as well as health care, and potentially during protracted drug therapy once drug resistance arises. We suggest that our strategy will be useful for keeping ahead in the drug resistance arms race.

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Mitotic Recombination Accelerates Adaptation in the Fungus Aspergillus nidulans

Cited by 113 publications

References 26 publications

Parasexuality and Ploidy Change in Candida tropicalis

Parasexuality and Ploidy Change in Candida tropicalis

Virulence and genetic diversity among isolates of Mycosphaerella fijiensis in two regions of Brazil

Using Aspergillus nidulans To Identify Antifungal Drug Resistance Mutations

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