Heterozygous diploid strains of Aspergillus nidulans: Enhanced virulence for mice in comparison to a prototrophic haploid strain

Purnell, Dallas M.; Martin, George M.

doi:10.1007/bf02050724

Cited by 12 publications

(12 citation statements)

References 12 publications

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“…Interestingly, none of the hybrid strains tested exhibited a higher level of pathogenicity than the haploid C. neoformans var. grubii strain, which thereby indicates that duplication of the C. neoformans genome does not enhance virulence, an observation which is similar to those made using C. albicans but unlike that of the increased virulence seen with some other fungi (26,43,51).…”

Section: Vol 70 2002supporting

confidence: 65%

“…Thus, Aspergillus nidulans and Beauveria bassiana and Beauveria sulfurescens hybrids are reported to be more virulent than the two haploid prototrophic or auxotrophic parents (43,51). Hubbard et al (26) found that a Candida albicans tetraploid strain was more virulent than its auxotrophic diploid parents, but its virulence does not exceed that of its prototrophic diploid parent.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Genetic Analyses of Mating Pheromones Reveal Intervariety Mating or Hybridization in Cryptococcus neoformans

Chaturvedi

Fan²,

Stein³

et al. 2002

Infect Immun

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The sexual mating of the pathogenic yeast Cryptococcus neoformans is important for pathogenesis studies because the fungal virulence is linked to the ␣ mating type (MAT␣). We characterized C. neoformans mating pheromones (MF␣ 1 and MFa1) from 122 strains to understand intervariety hybridization or mating and intervariety virulence. MF␣ 1 in three C. neoformans varieties showed (a) specific nucleotide polymorphisms, (b) different copy numbers and chromosomal localizations, and (c) unique deduced amino acids in two geographic populations of C. neoformans var. gattii. MF␣ 1 of different varieties cross-hybridized in Southern hybridizations. Their phylogenetic analyses showed purifying selection (neutral evolution). These observations suggested that MAT␣ strains from any of the three C. neoformans varieties could mate or hybridize in nature with MATa strains of C. neoformans var. neoformans. A few serotype A/D diploid strains provided evidence for mating or hybridization, while a majority of A/D strains tested positive for haploid MF␣ 1 identical to that of C. neoformans var. grubii. MF␣ 1 sequence and copy numbers in diploids were identical to those of C. neoformans var. grubii, while their MFa1 sequences were identical to those of C. neoformans var. neoformans; thus, these strains were hybrids. The mice survival curves and histological lesions revealed A/D diploids to be highly pathogenic, with pathogenicity levels similar to that of the C. neoformans var. grubii type strain and unlike the low pathogenicity levels of C. neoformans var. neoformans strains. In contrast to MF␣ 1 in three varieties, MFa1 amplicons and hybridization signals could be obtained only from two C. neoformans var. neoformans reference strains and eight A/D diploids. This suggested that a yet undiscovered MFa pheromone(s) in C. neoformans var. gattii and C. neoformans var. grubii is unrelated to, highly divergent from, or rarer than that in C. neoformans var. neoformans. These observations could form the basis for future studies on the role of intervariety mating in C. neoformans biology and virulence.Cryptococcus neoformans causes cryptococcal meningoencephalitis in healthy and immunocompromised individuals. The fungus has two mating types (mating type ␣ [MAT␣] and MATa), three varieties (C. neoformans var. neoformans, C. neoformans var. gattii, and C. neoformans var. grubii), and five serotypes (A, B, C, D, and A/D). C. neoformans var. grubii is most common in cryptococcosis among immunocompromised patients; the isolates are usually serotype A, MAT␣. This variety apparently reproduces asexually in nature, as indicated by the rarity of fertile MATa isolates (9,19,29). Sexual mating is seen in the laboratory both in C. neoformans var. neoformans (serotype D) and C. neoformans var. gattii (serotype B or C). The latter two varieties also show laboratory cross-hybridization; thus, their teleomorphs are classified as Filobasidiella neoformans var. neoformans and F. neoformans var. bacillispora (30). Currently, C. neoformans sexual mating is being ...

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Section: Vol 70 2002supporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Molecular Genetic Analyses of Mating Pheromones Reveal Intervariety Mating or Hybridization in Cryptococcus neoformans

Chaturvedi

Fan²,

Stein³

et al. 2002

Infect Immun

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“…However, in an alternative infection model, diploids were as virulent, if not more virulent, than corresponding haploid forms (Toffaletti et al 2004). In the rare human pathogen Aspergillus nidulans, a close relative of A. fumigatus, diploid strains were more virulent in mice than the corresponding haploid strains (Purnell and Martin 1973).…”

Section: Ploidy Shifts Via Sexual and Parasexual Cycles Ploidy Changementioning

confidence: 99%

Rapid Mechanisms for Generating Genome Diversity: Whole Ploidy Shifts, Aneuploidy, and Loss of Heterozygosity

Bennett

Forche

Berman

2014

Cold Spring Harbor Perspectives in Medicine

102

100

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“…Effects of ploidy on virulence could be species specific based on studies of other pathogenic fungi. For example, diploid Aspergillus nidulans strains are more virulent than the prototrophic haploid parent in mice (63), and some diploid hybrids between Beauveria bassiana and Beauveria sulfurescens are hypervirulent in insects (71). In contrast, tetraploid Candida albicans strains are similarly or less virulent than diploid strains (29,33,65).…”

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confidence: 99%

Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans

et al. 2008

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Hybridization with polyploidization is a significant biological force driving evolution. The effect of combining two distinct genomes in one organism on the virulence potential of pathogenic fungi is not clear. Cryptococcus neoformans, the most common cause of fungal infection of the central nervous system, has a bipolar mating system with a and ␣ mating types and occurs as A (haploid), D (haploid), and AD hybrid (mostly diploid) serotypes. Diploid AD hybrids are derived either from a-␣ mating or from unisexual mating between haploid cells. The precise contributions of increased ploidy, the effect of hybridization between serotypes A and D, and the combination of mating types to the virulence potential of AD hybrids have remained elusive. By using in vitro and in vivo characterization of laboratory-constructed isogenic diploids and AD hybrids with all possible mating type combinations in defined genetic backgrounds, we found that higher ploidy has a minor negative effect on virulence in a murine inhalation model of cryptococcosis. The presence of both mating types a and ␣ in AD hybrids did not affect the virulence potential, irrespective of the serotype origin. Interestingly, AD hybrids with only one mating type behaved differently, with the virulence of ␣AD␣ strains similar to that of other hybrids, while aADa hybrids displayed significantly lower virulence due to negative epistatic interactions between the Aa and Da alleles of the mating type locus. This study provides insights into the impact of ploidy, mating type, and serotype on virulence and the impact of hybridization on the fitness and virulence of a eukaryotic microbial pathogen.

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Heterozygous diploid strains of Aspergillus nidulans: Enhanced virulence for mice in comparison to a prototrophic haploid strain

Cited by 12 publications

References 12 publications

Molecular Genetic Analyses of Mating Pheromones Reveal Intervariety Mating or Hybridization in Cryptococcus neoformans

Molecular Genetic Analyses of Mating Pheromones Reveal Intervariety Mating or Hybridization in Cryptococcus neoformans

Rapid Mechanisms for Generating Genome Diversity: Whole Ploidy Shifts, Aneuploidy, and Loss of Heterozygosity

Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans

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