Ploidy dynamics and evolvability in fungi

Wertheimer, Noa; Stone, Neil

doi:10.1098/rstb.2015.0461

Cited by 44 publications

(48 citation statements)

References 115 publications

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“…8) (29). Importantly, numerous rearrangements of Ch5, including trisomy of the entire Ch5 or large portions of Ch5 as well as duplication of the left arm, were recently found in clinical isolates (30)(31)(32).…”

Section: Fig 8 Map Of Ch5mentioning

confidence: 99%

Tolerance to Caspofungin in Candida albicans Is Associated with at Least Three Distinctive Mechanisms That Govern Expression of FKS Genes and Cell Wall Remodeling

Yang

Zhang

Wakabayashi

et al. 2017

Antimicrob Agents Chemother

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Expanding echinocandin use to prevent or treat invasive fungal infections has led to an increase in the number of breakthrough infections due to resistant Candida species. Although it is uncommon, echinocandin resistance is well documented for Candida albicans, which is among the most prevalent bloodstream organisms. A better understanding is needed to assess the cellular factors that promote tolerance and predispose infecting cells to clinical breakthrough. We previously showed that some mutants that were adapted to growth in the presence of toxic sorbose due to loss of one chromosome 5 (Ch5) also became more tolerant to caspofungin. We found here, following direct selection of mutants on caspofungin, that tolerance can be conferred by at least three mechanisms: (i) monosomy of Ch5, (ii) combined monosomy of the left arm and trisomy of the right arm of Ch5, and (iii) an aneuploidyindependent mechanism. Tolerant mutants possessed cell walls with elevated chitin and showed downregulation of genes involved in cell wall biosynthesis, namely, FKS, located outside Ch5, and CHT2, located on Ch5, irrespective of Ch5 ploidy. Also irrespective of Ch5 ploidy, the CNB1 and MID1 genes on Ch5, which are involved in the calcineurin signaling pathway, were expressed at the diploid level. Thus, multiple mechanisms can affect the relative expression of the aforementioned genes, controlling them in similar ways. Although breakthrough mutations in two specific regions of FKS1 have previously been associated with caspofungin resistance, we found mechanisms of caspofungin tolerance that are independent of FKS1 and thus represent an earlier event in resistance development.

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Section: Fig 8 Map Of Ch5mentioning

confidence: 99%

Tolerance to Caspofungin in Candida albicans Is Associated with at Least Three Distinctive Mechanisms That Govern Expression of FKS Genes and Cell Wall Remodeling

Yang

Zhang

Wakabayashi

et al. 2017

Antimicrob Agents Chemother

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“…Polyploidy and complex aneuploidy play a major role in the capability of fungal pathogens to adapt to various stresses and to the changing condition within host niches. 10,11 These overall genome shifts in chromosome number have been characterized as drivers of increased genetic diversity in Cryptococcus neoformans, Candida albicans, and also for Candida lusitaniae -a close relative of C. auris . 20-25…”

Section: Resultsmentioning

confidence: 99%

Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

Ruiz

Ross

Schelenz

et al. 2019

Preprint

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Candida auris is a newly emerging pathogenic microbe, having been identified as a medically relevant fungus as recently as 2009. It is the most drug-resistant yeast species known to date and its emergence and population structure are unusual. Because of its recent emergence we are largely ignorant about fundamental aspects of its general biology, life cycle, and population dynamics. Here we report the karyotype variability of 26 C. auris strains representing the four main clades. We demonstrate that all strains are haploid and have a highly plastic karyotype containing five to seven chromosomes, which can undergo marked alterations within a short time-frame when the fungus is put under genotoxic, heat, or osmotic stress. No simple correlation was found between karyotype pattern, drug resistance, and clade affiliation indicating that karyotype heterogeneity is rapidly evolving. As with other Candida species, these marked karyotype differences between isolates are likely to have an important impact on pathogenic traits of C. auris.Introduction 1 A current, major concern in medical mycology is the emergence of the multidrug-resistant 2 pathogen Candida auris. This species was named according to its first identification as an isolate 3 from the ear canal of a Japanese patient in 2009. 1 Since then, it has rapidly become a major 4 healthcare threat with hospital outbreaks occurring worldwide. [2][3][4] Most C. auris isolates also 5 show high levels of resistance to antifungal drugs, including azoles, echinocandins, 5-flucytosine, 6 and polyenes (amphotericin B). 5,6 C. auris is also difficult to eradicate from hospital intensive 7 care wards and as a skin colonizer it can apparently be transmitted from patient to patient. 4 8 Whole genome sequencing (WGS) of C. auris isolates has indicated that there are at least 9 four distinct geographical clades of this species; East Asia (Japan, Korea), South Asia (India, 10 Pakistan), South Africa, and South America (Venezuela). 6 Clades differ by tens of thousands of 11 single nucleotide polymorphisms (SNPs) from each other, however, within each clade isolates 12 are almost indistinguishable from each other on a DNA sequence level. 5-7 This suggests that the 13 C. auris population structure is characterized by distinct and highly variable clades that are 14 distributed worldwide and almost non-variable clonal expansions of a single genotype within 15 individual outbreaks. 3,4 The origin(s) of the strong variability between and the minor variability 16 within clades are currently unknown. 17 Polyploidy, aneuploidy, and gross chromosome rearrangements have been recognized 18 drivers of genetic diversity in pathogenic and non-pathogenic fungi for some time. 8-12 In 19 pathogenic yeasts, such as C. albicans, mechanisms for ploidy shifts and chromosome 20 rearrangements have been described, and their importance for adaptation to environmental 21 stresses and host niches, as well as for developing resistance to antifungal drugs has been 22 identified. 13-17 23Here, we characteri...

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“…The C. albicans genome is highly plastic and high levels of heterozygosity, intra-chromosome recombination and aneuploidy can be observed between genomes of different strains. The loss of heterozygosity, chromosomal rearrangements and whole chromosome or segmental aneuploidies lead to stress adaptation and can also affect drug sensitivity by influencing the copy number of key drugresistance alleles [4]. Many key virulence-associated functions are performed by multi-gene families, some of which have evolved by sub-telomeric gene duplication and expansion.…”

Section: Genome and Evolutionmentioning

confidence: 99%

Microbe Profile: Candida albicans: a shape-changing, opportunistic pathogenic fungus of humans

2017

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Graphical abstract(a) Morphotypes of Candida albicans (blue sector, vegetative forms; pink sector, forms related to mating or changes in ploidy). Cell types shown include: budding yeast cells; elongated conjoined yeasts forming pseudohyphae; parallel-sided hyphae; chlamydospores formed from suspensor cells; enlarged goliath cells formed under zinc deprivation (unpublished study, image from Duncan Wilson); intestinal gut form cells (image from Suzanne Noble); mating competence defined by whitegrey-opaque cell transitions (images from Guanghua Huang); elongated chemotactic shmoo-mating projections leading to tetraploid zygote formation (images from David Soll and Karla Daniels); trimera formed by unequal chromosome segregation under antifungal exposure (image from Judith Berman). (b) Superficial yeast colonization and invasion of the chicken chorioallantoic membrane by C. albicans hyphal cells. AbstractCandida albicans is normally a harmless commensal of human beings, but it can cause superficial infections of the mucosa (oral/vaginal thrush) in healthy individuals and (rarely) infections of the skin or nails. It can also become invasive, causing life-threatening systemic and bloodstream infections in immunocompromised hosts, where the mortality rate can be as high as 50 %. It is the most common cause of serious fungal infection and is a common cause of nosocomial infections in hospitals. Some strains have been recognized that are resistant to azoles or echinocandins, which are the first-line antifungals for treatment of C. albicans infections.

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Ploidy dynamics and evolvability in fungi

Cited by 44 publications

References 115 publications

Tolerance to Caspofungin in Candida albicans Is Associated with at Least Three Distinctive Mechanisms That Govern Expression of FKS Genes and Cell Wall Remodeling

Tolerance to Caspofungin in Candida albicans Is Associated with at Least Three Distinctive Mechanisms That Govern Expression of FKS Genes and Cell Wall Remodeling

Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

Microbe Profile: Candida albicans: a shape-changing, opportunistic pathogenic fungus of humans

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