Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the
            <i>Cryptococcus</i>
            Genus

Hagen, Ferry; Lumbsch, H. Thorsten; Arsenijevic, Valentina Arsić; Badali, Hamid; Bertout, Sébastien; Billmyre, R. Blake; Bragulat, M.R.; Cabañes, F. Javier; Carbia, Mauricio; Chakrabarti, Arunaloke; Chaturvedi, Sudha; Chen, Min; Chowdhary, Anuradha; Colom, María Francisca; Cornely, Oliver A.; Crous, Pedro W.; Cuétara, María Soledad; Diaz, Mara R.; Espinel-Ingroff, Ana; Fakhim, Hamed; Falk, Rama; Fang, Wenjie; Herkert, Patricia Fernanda; Rodríguez, Consuelo Ferrer; Fraser, James A.; Gené, Josepa; Guarro, Josep; Idnurm, Alexander; Illnait-Zaragozí, María Teresa; Khan, Ziauddin; Khayhan, Kantarawee; Kolecka, Anna; Kurtzman, Cletus P.; Lagrou, Katrien; Liao, Wanqing; Linares, Carlos Eduardo Blanco; Meis, Jacques F.; Nielsen, Kirsten; Nyazika, Tinashe K.; Pan, Weihua; Pekmezović, Marina; Polacheck, Itzhack; Posteraro, Brunella; Filho, Flávio de Queiroz Telles; Romeo, Orazio; Sánchez, Manuel; Sampaio, Ana; Sriburee, Pojana; Sugita, Takashi; Taj-Aldeen, Saad J.; Takashima, Masako; Taylor, John W.; Theelen, Bart; Tomazin, Rok; Verweij, Paul E.; Wahyuningsih, Retno; Wang, Ping; Boekhout, Teun

doi:10.1128/msphere.00238-17

Cited by 120 publications

(94 citation statements)

References 148 publications

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“…Recently, it was suggested that some of these major molecular types should be raised to species level (Hagen et al, 2015). However, the proposed division of these complexes into seven distinct species is still the subject of debate (Hagen et al, 2017;Kwon-Chung et al, 2017) and a recent publication has shown that this proposal is premature (Cogliati et al, 2019). To maintain taxonomic stability, the use of "species complexes" had been proposed as interim solution (Kwon-Chung et al, 2017) and is used herein.…”

Section: Introductionmentioning

confidence: 99%

The mycobiome of Australian tree hollows in relation to the Cryptococcus gattii and C. neoformans species complexes

Irinyi

Malík

Powell

et al. 2019

Ecology and Evolution

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Cryptococcosis is a fungal infection caused by members of the Cryptococcus gattii and C. neoformans species complexes. The C. gattii species complex has a strong environmental association with eucalypt hollows (particularly Eucalyptus camaldulensis), which may present a source of infection. It remains unclear whether a specific mycobiome is required to support its environmental survival and growth. Conventional detection of environmental Cryptococcus spp. involves culture on differential media, such as Guizotia abyssinica seed agar. Next‐generation sequencing (NGS)‐based culture‐independent identification aids in contextualising these species in the environmental mycobiome. Samples from 23 Australian tree hollows were subjected to both culture‐ and amplicon‐based metagenomic analysis to characterize the mycobiome and assess relationships between Cryptococcus spp. and other fungal taxa. The most abundant genera detected were Coniochaeta, Aspergillus, and Penicillium, all being commonly isolated from decaying wood. There was no correlation between the presence of Cryptococcus spp. in a tree hollow and the presence of any other fungal genus. Some differences in the abundance of numerous taxa were noted in a differential heat tree comparing samples with or without Cryptococcus‐NGS reads. The study expanded the known environmental niche of the C. gattii and C. neoformans species complexes in Australia with detections from a further five tree species. Discrepancies between the detection of Cryptococcus spp. using culture or NGS suggest that neither is superior per se and that, rather, these methodologies are complementary. The inherent biases of amplicon‐based metagenomics require cautious interpretation of data through consideration of its biological relevance.

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Section: Introductionmentioning

confidence: 99%

The mycobiome of Australian tree hollows in relation to the Cryptococcus gattii and C. neoformans species complexes

Irinyi

Malík

Powell

et al. 2019

Ecology and Evolution

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“…It was proposed that C. neoformans should be divided into two species, and C. gattii be divided into five species according to the phylogenetic analysis of 155 isolates (Hagen et al ., ). However, studies with more isolates or analysing more genomes may reveal different classification, and the consensus about the classification system has not been reached yet (Hagen et al ., ; Kwon‐Chung et al ., ). Some authors proposed to use ‘ Cryptococcus neoformans species complex’ and ‘ Cryptococcus gattii species complex,’ which can recognize diversity without confusion (Kwon‐Chung et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Two‐step method for isolating Cryptococcus species complex from environmental material using a new selective medium

Lin

Chung

2019

Environ Microbiol Rep

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Summary Cryptococcosis is an opportunistic infection caused by the Cryptococcus species complex. An outbreak of cryptococcosis caused by Cryptococcus gattii (AFLP6/VGII) in North America has indicated the need for studies of this organism and its environmental niche. Difficulties in isolating the Cryptococcus spp. because of the overgrowth of filamentous fungi onto culture media and its low fungal population size under natural conditions limit studies of these pathogenic yeasts. We designed a selective medium that inhibits the growth of environmental filamentous fungi but does not inhibit that of Cryptococcus cells. After enrichment in acidified YPD media and inoculation onto selective media, Cryptococcus cells in brown‐coloured colonies were isolated from environmental materials. This two‐step method is useful for isolating environmental members of the Cryptococcus species complex, which is essential for further studies involving diversity and the microbe–environment relationship of this yeast.

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“…Four of the six gene deletions that impacted 17 murine survival were novel. Such bedside-to-bench translational research provides important 18 candidate genes for future studies on virulence-associated traits in human Cryptococcus 19 infections.Even with the best available care, mortality rates in cryptococcal meningitis range from 23 20-60%. Disease is often due to infection by the fungus Cryptococcus neoformans and involves a 24 complex interaction between the human host and the fungal pathogen.…”

mentioning

confidence: 99%

“…These analyses have led to 70 competing species definition proposals. The first proposes classifying strains into seven species 71(two from C. neoformans following the serotypes and five from C. gattii) [18,19]. However, 72 based on an analysis of 2600 strains, which revealed genetic diversity that is not-wholly captured 73 by the seven species proposal [20] the second wants to maintain two groups, delineated as the 74 "C. neoformans species complex" and the "C. gattii species complex" [21].…”

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confidence: 99%

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Identification of pathogen genomic differences that impact human immune response and disease duringCryptococcus neoformansinfection

Gerstein

Jackson

McDonald

et al. 2019

Preprint

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1 2Patient outcomes during infection are due to a complex interplay between the quality of medical 3 care, host immunity factors, and the infecting pathogen's characteristics. To probe the influence 4 of pathogen genotype on human immune response and disease, we examined Cryptococcus 5 neoformans isolates collected during the Cryptococcal Optimal ART Timing (COAT) trial in 6 Uganda. We measured human participants' immunologic phenotypes, meningitis disease 7 parameters, and survival. We compared this clinical data to whole genome sequences from 38 C. 8 neoformans isolates of the most frequently observed sequence type (ST) ST93 in our Ugandan 9 participant population, and an additional 18 strains from 9 other sequence types representing the 10 known genetic diversity within the Ugandan Cryptococcus clinical isolates. We focused our 11 analyses on 652 polymorphisms that: were variable among the ST93 genomes, were not in 12 centromeres or extreme telomeres, and were predicted to have a fitness effect. Logistic 13 regression and principal component analyses identified 40 candidate Cryptococcus genes and 3 14 hypothetical RNAs associated with human immunologic response or clinical parameters. We 15 infected mice with 17 available KN99α gene deletion strains for these candidate genes and found 16 that 35% (6/17) directly influenced murine survival. Four of the six gene deletions that impacted 17 murine survival were novel. Such bedside-to-bench translational research provides important 18 candidate genes for future studies on virulence-associated traits in human Cryptococcus 19 infections.Even with the best available care, mortality rates in cryptococcal meningitis range from 23 20-60%. Disease is often due to infection by the fungus Cryptococcus neoformans and involves a 24 complex interaction between the human host and the fungal pathogen. Although previous studies 25 have suggested genetic differences in the pathogen impact human disease, it has proven quite 26 difficult to identify the specific C. neoformans genes that impact the outcome of the human 27 infection. Here, we take advantage of a Ugandan patient cohort infected with closely related C. 28 neoformans strains to examine to role of pathogen genetic variants on several human disease 29 characteristics. Using a pathogen whole genome sequencing approach, we showed that 40 C. 30neoformans genes are associated with human disease. Surprisingly, many of these genes are 31 specific to Cryptococcus and have unknown functions. We also show deletion of these genes 32 alters disease in a mouse model of infection, confirming their role in disease. These findings are 33 particularly important because they are the first to identify C. neoformans genes associated with 34 human cryptococcal meningitis and lay the foundation for future studies that may lead to new 35 treatment strategies aimed at reducing patient mortality. 36 37 38Cryptococcus neoformans is the etiological agent of cryptococcal meningitis, the most 39 common brain infection in Sub-Saharan Africa, which enc...

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Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the Cryptococcus Genus

Abstract: Cryptococcosis is a major fungal disease caused by members of the Cryptococcus gattii and Cryptococcus neoformans species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made.

Cited by 120 publications

References 148 publications

The mycobiome of Australian tree hollows in relation to the Cryptococcus gattii and C. neoformans species complexes

The mycobiome of Australian tree hollows in relation to the Cryptococcus gattii and C. neoformans species complexes

Two‐step method for isolating Cryptococcus species complex from environmental material using a new selective medium

Identification of pathogen genomic differences that impact human immune response and disease duringCryptococcus neoformansinfection

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