Interaction Between Genetic Background and the Mating-Type Locus in <i>Cryptococcus neoformans</i> Virulence Potential

Nielsen, Kirsten; Marra, Robert E.; Hagen, Ferry; Boekhout, Teun; Mitchell, Thomas G.; Cox, Gary M.; Heitman, Joseph

doi:10.1534/genetics.105.045039

Cited by 82 publications

(79 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, congenic ␣ and a cells (genetically identical except at the mating type locus) of both serotype A and serotype D strains grow equally well under various laboratory conditions. Congenic ␣ and a strains in the serotype A H99 background display the same pathogenicity level in various invertebrate and mammalian models (56,57), and the same is true for congenic ␣ and a strains in the serotype D B3501 background (58). However, in some backgrounds or under certain conditions, the ␣ mating type locus may enhance virulence.…”

mentioning

confidence: 88%

“…Animals were infected essentially as previously described (58). Six-to 8-week-old female DBA mice were inoculated with 1 ϫ 10 6 fungal cells in 50 l of PBS in the lateral tail vein.…”

Section: Murine Inhalation Model Of Cryptococcosis and Recovery Of Fumentioning

confidence: 99%

“…For example, nonisogenic ␣ strains in general were found to be more virulent than a strains (3,36,44). ␣ strains in the serotype D strain JEC21 and NIH433 backgrounds are more virulent than congenic a strains in a murine model of cryptococcosis (41,58), and ␣ cells in the serotype A strain H99 background preferentially disseminate to the central nervous system during coinfection with congenic a cells (56).…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2008

Self Cite

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 88%

“…Animals were infected essentially as previously described (58). Six-to 8-week-old female DBA mice were inoculated with 1 ϫ 10 6 fungal cells in 50 l of PBS in the lateral tail vein.…”

Section: Murine Inhalation Model Of Cryptococcosis and Recovery Of Fumentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…James et al hypothesized that the current clonal epidemic may be a result of strong selection on a single genotype, essentially a single mating type resulting in the elimination of the opposite mating type (125). Several examples of a specific mating type being both more common and more virulent than its partner exist for other fungal species, such as C. neoformans (213,214,217).…”

Section: Batrachochytrium Dendrobatidis: An Emerging Amphibian Pathogenmentioning

confidence: 99%

The Evolution of Sex: a Perspective from the Fungal Kingdom

Lee

et al. 2010

Microbiol Mol Biol Rev

Self Cite

323

344

View full text Add to dashboard Cite

SUMMARY Sex is shrouded in mystery. Not only does it preferentially occur in the dark for both fungi and many animals, but evolutionary biologists continue to debate its benefits given costs in light of its pervasive nature. Experimental studies of the benefits and costs of sexual reproduction with fungi as model systems have begun to provide evidence that the balance between sexual and asexual reproduction shifts in response to selective pressures. Given their unique evolutionary history as opisthokonts, along with metazoans, fungi serve as exceptional models for the evolution of sex and sex-determining regions of the genome (the mating type locus) and for transitions that commonly occur between outcrossing/self-sterile and inbreeding/self-fertile modes of reproduction. We review here the state of the understanding of sex and its evolution in the fungal kingdom and also areas where the field has contributed and will continue to contribute to illuminating general principles and paradigms of sexual reproduction.

show abstract

“…Monokaryotic fruiting, once thought to be mitotic and asexual, has been demonstrated to be a modified form of sexual reproduction occurring between strains of the same mating type and is most commonly observed in a strains but can also occur with a isolates Lin et al , 2007. Because a isolates predominate (.95%) in most naturally occurring C. neoformans populations, and the a mating type is linked to virulence (Kwon-Chung and Bennett 1978;Nielsen et al 2005;Lin et al 2006;Lin 2009), the discovery of a-a unisexual reproduction (samesex mating) suggests how infectious spores can be produced by this almost unisexual pathogen. Although many similarities are shared between opposite-sex and same-sex mating, ongoing studies comparing the underlying mechanisms provide insight into how same-sex mating can contribute in unique ways to the fitness of these pathogenic fungi (Lee et al 2010;Wang and Lin 2011).…”

mentioning

confidence: 99%

Sex-Induced Silencing Operates During Opposite-Sex and Unisexual Reproduction in Cryptococcus neoformans

2013

Self Cite

View full text Add to dashboard Cite

Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from yeast to hyphae during a-a opposite-sex mating and a-a unisexual reproduction (same-sex mating). Infectious spores are generated during both processes. We previously identified a sex-induced silencing (SIS) pathway in the C. neoformans serotype A var. grubii lineage, in which tandem transgene arrays trigger RNAi-dependent gene silencing at a high frequency during a-a opposite-sex mating, but at an 250-fold lower frequency during asexual mitotic vegetative growth. Here we report that SIS also operates during a-a unisexual reproduction. A self-fertile strain containing either SXI2a-URA5 or NEO-URA5 transgene arrays exhibited an elevated silencing frequency during solo and unisexual mating compared with mitotic vegetative growth. We also found that SIS operates at a similar efficiency on transgene arrays of the same copy number during either a-a unisexual reproduction or a-a opposite-sex mating. URA5-derived small RNAs were detected in the silenced progeny of a-a unisexual reproduction and RNAi core components were required, providing evidence that SIS induced by same-sex mating is also mediated by RNAi via sequence-specific small RNAs. In addition, our data show that the SIS RNAi pathway also operates to defend the genome via squelching transposon activity during same-sex mating as it does during opposite-sex mating. Taken together, our results confirm that SIS is conserved between the divergent C. neoformans serotype A and serotype D cryptic sibling species. COMPLEX genomes have evolved sophisticated mechanisms to sense the presence, and to control the behavior of genomic invaders such as transposable elements and viruses. Among a panoply of diverse strategies, homologydependent gene silencing (HDGS) is a ubiquitous phenomenon among fungi, plants, and animals (Cogoni 2001). HDGS, also known as cosuppression, was first found to be triggered by transgenes, viruses, or unusual duplications of endogenous genes in both plants and fungi (Cogoni et al. 1996;English et al. 1996;Bingham 1997;Cogoni and Macino 1999a). Although a broad variety of HDGS phenomena are known, all of these gene silencing processes are based on the recognition of nucleic acid sequence homology, followed by inactivation of homologous sequences. Gene silencing can occur at a transcriptional or post-transcriptional level involving sequence-specific mRNA degradation. The most studied and best-characterized HDGS phenomenon in fungi is a process known as quelling, which occurs in Neurospora crassa vegetative tissue (Cogoni et al. 1996). Quelling is an RNAi-mediated silencing mechanism that post-transcriptionally inactivates duplicated sequences, in many cases resulting from introduction of transgenes. In quelling, the silenced loci can act in trans, leading to silencing of all homologous genes throughout the genome. The core RNAi components, including Argonaute, Dicer-like proteins, and RNA-dependent RNA polymerase (RdRP), are all required for quellin...

show abstract

Interaction Between Genetic Background and the Mating-Type Locus in Cryptococcus neoformans Virulence Potential

Cited by 82 publications

References 42 publications

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

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

The Evolution of Sex: a Perspective from the Fungal Kingdom

Sex-Induced Silencing Operates During Opposite-Sex and Unisexual Reproduction in Cryptococcus neoformans

Contact Info

Product

Resources

About