Impact of Mating Type, Serotype, and Ploidy on the Virulence of
            <i>Cryptococcus neoformans</i>

Lin, Xiaorong; Nielsen, Kirsten; Patel, Sweta; Heitman, Joseph

doi:10.1128/iai.00168-08

Cited by 78 publications

(98 citation statements)

References 82 publications

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“…However, other studies suggest that ␣ isolates in general are more virulent than a strains (12,126,145). Recently, Lin et al (151) carried out a detailed analysis to investigate the effect of ploidy and mating type on virulence of serotype A and serotype AD isolates. Somewhat surprisingly, they found that diploid isolates are slightly less virulent than haploid isolates in a murine inhalation model.…”

Section: Cryptococcus Neoformansmentioning

confidence: 99%

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Fungal Sex and Pathogenesis

Butler

2010

Clin Microbiol Rev

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SUMMARYHuman fungal pathogens are associated with diseases ranging from dandruff and skin colonization to invasive bloodstream infections. The major human pathogens belong to theCandida,Aspergillus, andCryptococcusclades, and infections have high and increasing morbidity and mortality. Many human fungal pathogens were originally assumed to be asexual. However, recent advances in genome sequencing, which revealed that many species have retained the genes required for the sexual machinery, have dramatically influenced our understanding of the biology of these organisms. Predictions of a rare or cryptic sexual cycle have been supported experimentally for some species. Here, I examine the evidence that human pathogens reproduce sexually. The evolution of the mating-type locus in ascomycetes (includingCandidaandAspergillusspecies) and basidiomycetes (MalasseziaandCryptococcus) is discussed. I provide an overview of how sex is suppressed in different species and discuss the potential associations with pathogenesis.

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Section: Cryptococcus Neoformansmentioning

confidence: 99%

“…They are also primary pathogens and a cause of pulmonary disease (201). The majority of clinical isolates (up to 95% of human infections) are serotype A, which are also more virulent in animal models (151).…”

Section: Cryptococcus Neoformansmentioning

confidence: 99%

Fungal Sex and Pathogenesis

Butler

2010

Clin Microbiol Rev

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“…Phenotypic assays were performed as described previously (37). Briefly, strains to be tested were grown overnight in YPD liquid medium.…”

Section: Figmentioning

confidence: 99%

A Family of Secretory Proteins Is Associated with Different Morphotypes in Cryptococcus neoformans

Gyawali

Upadhyay

Way

et al. 2017

Appl Environ Microbiol

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Cryptococcus neoformans, an opportunistic human fungal pathogen, can undergo a yeast-to-hypha transition in response to environmental cues. This morphological transition is associated with changes in the expression of cell surface proteins. The Cryptococcus cell surface and secreted protein Cfl1 was the first identified adhesin in the Basidiomycota. Cfl1 has been shown to regulate morphology, biofilm formation, and intercellular communication. Four additional homologs of CFL1 are harbored by the Cryptococcus genome: DHA1, DHA2, CPL1, and CFL105. The common features of this gene family are the conserved C-terminal SIGC domain and the presence of an N-terminal signal peptide. We found that all these Cfl1 homolog proteins are indeed secreted extracellularly. Interestingly, some of these secretory proteins display cell type-specific expression patterns: Cfl1 is hypha specific, Dha2 is yeast specific, and Dha1 (delayed hypersensitivity antigen 1) is expressed in all cell types but is particularly enriched at basidia. Interestingly, Dha1 is induced by copper limitation and suppressed by excessive copper in the medium. This study further attests to the physiological heterogeneity of the Cryptococcus mating colony, which is composed of cells with heterogeneous morphotypes. The differential expression of these secretory proteins contributes to heterogeneity, which is beneficial for the fungus to adapt to changing environments. IMPORTANCE Heterogeneity in physiology and morphology is an important bethedging strategy for nonmobile microbes such as fungi to adapt to unpredictable environmental changes. Cryptococcus neoformans, a ubiquitous basidiomycetous fungus, is known to switch from the yeast form to the hypha form during sexual development. However, in a mating colony, only a subset of yeast cells switch to hyphae, and only a fraction of the hyphal subpopulation will develop into fruiting bodies, where meiosis and sporulation occur. Here, we investigated a basidiomycete-specific secretory protein family. We found that some of these proteins are cell type specific, thus contributing to the heterogeneity of a mating colony. Our study also demonstrates the importance of examining the protein expression pattern at the individual-cell level in addition to population gene expression profiling for the investigation of a heterogeneous community.KEYWORDS dimorphism, morphogenesis, morphotype, secretory proteins, sexual reproduction A dhesins are cell surface proteins that are required for microbes to adhere to the substrate as well as to other cells (1-3). Adhesins in pathogenic fungi play a role in a wide variety of functions, such as host-pathogen interactions, biofilm formation, filamentation, and mating (2, 4, 5). The expression of adhesins is responsive to environmental cues (1). For instance, adhesins of Saccharomyces (Flo proteins) are activated during nitrogen or carbon source starvation, and they are required for cell-cell adherence and cell-substrate adherence (6-8). Many fungal adhesins show a cell type-spec...

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“…The in vitro phenotypic assays were performed as previously described (31,35). Briefly, yeast cells were grown on YPD medium overnight and washed three times with water.…”

Section: Figmentioning

confidence: 99%

“…1), also exhibit low levels of virulence in an intravenous infection model of murine cryptococcosis (33). Studying cryptococcal virulence with these serotype D congenic pairs often requires long study periods (40 to ϳϾ100 days), unnatural intravenous inoculation, and relatively high infection doses (1 ϫ 10 6 to ϳ1 ϫ 10 7 cells/mouse) (27,(32)(33)(34)(35). The construction of the H99 congenic pair strains (KN99␣/ KN99a) facilitated genetic analyses in the serotype A background.…”

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confidence: 99%

Congenic Strains of the Filamentous Form of Cryptococcus neoformans for Studies of Fungal Morphogenesis and Virulence

et al. 2013

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cCryptococcus neoformans is an unconventional dimorphic fungus that can grow either as a yeast or in a filamentous form. To facilitate investigation of genetic factors important for its morphogenesis and pathogenicity, congenic a and ␣ strains for a filamentous form were constructed. XL280 (␣) was selected as the background strain because of its robust ability to undergo the morphological transition from yeast to the filamentous form. The MATa allele from a sequenced strain JEC20 was introgressed into the XL280 background to generate the congenic a and ␣ pair strains. The resulting congenic strains were then used to test the impact of mating type on virulence. In both the inhalation and the intravenous infection models of murine cryptococcosis, the congenic a and ␣ strains displayed comparable levels of high virulence. The a-␣ coinfections displayed equivalent virulence to the individual a or ␣ infections in both animal models. Further analyses of the mating type distribution in a-␣ coinfected mice suggested no influence of a-␣ interactions on cryptococcal neurotropism, irrespective of the route of inoculation. Furthermore, deletion or overexpression of a known transcription factor, Znf2, in XL280 abolished or enhanced filamentation and biofilm formation, consistent with its established role. Overexpression of Znf2 in XL280 led to attenuation of virulence and a reduced abundance in the brain but not in other organs, suggesting that Znf2 might interfere with cryptococcal neurotropism upon extrapulmonary dissemination. In summary, the congenic strains provide a new resource for the exploration of the relationship in Cryptococcus between cellular morphology and pathogenesis.

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

Cited by 78 publications

References 82 publications

Fungal Sex and Pathogenesis

Fungal Sex and Pathogenesis

A Family of Secretory Proteins Is Associated with Different Morphotypes in Cryptococcus neoformans

Congenic Strains of the Filamentous Form of Cryptococcus neoformans for Studies of Fungal Morphogenesis and Virulence

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