scholarly journals The Case for Adopting the “Species Complex” Nomenclature for the Etiologic Agents of Cryptococcosis

mSphere ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Kyung J. Kwon-Chung ◽  
John E. Bennett ◽  
Brian L. Wickes ◽  
Wieland Meyer ◽  
Christina A. Cuomo ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Analysis ◽  
Cryptococcus Neoformans ◽  
Species Complex ◽  
Intermediate Step ◽  
Separate Species ◽  
Content Type ◽  
Etiologic Agents ◽  
Genotypic Characteristics ◽  
Biological Differences

ABSTRACT Cryptococcosis is a potentially lethal disease of humans/animals caused by Cryptococcus neoformans and Cryptococcus gattii. Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed that C. neoformans be divided into two species and C. gattii into five species based on a phylogenetic analysis of 115 isolates. While this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the published genotypes of 2,606 strains have already revealed more genetic diversity than is encompassed by seven species. Naming every clade as a separate species at this juncture will lead to continuing nomenclatural instability. In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, we recommend using “Cryptococcus neoformans species complex” and “C. gattii species complex” as a practical intermediate step, rather than creating more species. This strategy recognizes genetic diversity without creating confusion.

scholarly journals Multicenter Study of Isavuconazole MIC Distributions and Epidemiological Cutoff Values for the Cryptococcus neoformans-Cryptococcus gattii Species Complex Using the CLSI M27-A3 Broth Microdilution Method

2014 ◽  
Vol 59 (1) ◽  
pp. 666-668 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chowdhary ◽  
G. M. Gonzalez ◽  
J. Guinea ◽  
F. Hagen ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Multicenter Study ◽  
Species Complex ◽  
Cryptococcus Gattii ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
Microdilution Method ◽  
Cutoff Values ◽  
Broth Microdilution Method

ABSTRACTEpidemiological cutoff values (ECVs) of isavuconazole are not available forCryptococcusspp. The isavuconazole ECVs based on wild-type (WT) MIC distributions for 438Cryptococcus neoformansnongenotyped isolates, 870 isolates of genotype VNI, and 406Cryptococcus gattiiisolates from six laboratories and different geographical areas were 0.06, 0.12, and 0.25 μg/ml, respectively. These ECVs may aid in detecting non-WT isolates with reduced susceptibilities to isavuconazole.

scholarly journals Molecular Epidemiology Reveals Genetic Diversity amongst Isolates of the Cryptococcus neoformans/C. gattii Species Complex in Thailand

2013 ◽  
Vol 7 (7) ◽  
pp. e2297 ◽  
Author(s):  
Sirada Kaocharoen ◽  
Popchai Ngamskulrungroj ◽  
Carolina Firacative ◽  
Luciana Trilles ◽  
Dumrongdej Piyabongkarn ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Molecular Epidemiology ◽  
Cryptococcus Neoformans ◽  
Species Complex

scholarly journals The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G 2 Arrest in Cryptococcus

mBio ◽  
2021 ◽  
Author(s):  
Sophie Altamirano ◽  
Zhongming Li ◽  
Man Shun Fu ◽  
Minna Ding ◽  
Sophie R. Fulton ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Cell Cycle ◽  
Cryptococcus Neoformans ◽  
Genetic Diseases ◽  
Cell Formation ◽  
Host Adaptation ◽  
Content Type ◽  
Natural Mechanism

Dysregulation of the cell cycle underlies many human genetic diseases and cancers, yet numerous organisms, including microbes, also manipulate the cell cycle to generate both morphologic and genetic diversity as a natural mechanism to enhance their chances for survival. The eukaryotic pathogen Cryptococcus neoformans generates morphologically distinct polyploid titan cells critical for host adaptation and subsequent disease.

scholarly journals Genetic and genomic analyses reveal boundaries between species closely related to Cryptococcus pathogens

2019 ◽  
Author(s):  
Andrew Ryan Passer ◽  
Marco A. Coelho ◽  
Robert Blake Billmyre ◽  
Minou Nowrousian ◽  
Moritz Mittelbach ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Genome Sequencing ◽  
Evolutionary Biology ◽  
Species Complex ◽  
Biological Diversity ◽  
Sequence Divergence ◽  
Biological Species ◽  
Cryptococcus Gattii ◽  
Small Scale ◽  
Separate Species

AbstractSpeciation is a central mechanism of biological diversification. While speciation is well studied in plants and animals, in comparison, relatively little is known about speciation in fungi. One fungal model is the Cryptococcus genus, which is best known for the pathogenic Cryptococcus neoformans/Cryptococcus gattii species complex that causes over 200,000 new infections in humans annually. The closest non-human pathogenic relatives are the sibling species, Cryptococcus amylolentus and Tsuchiyaea wingfieldii. However, because relatively few isolates of each species are available, it is unclear whether they represent divergent lineages of the same species or different biological species. The recent isolation of an additional strain, preliminarily identified as T. wingfieldii, prompted us to reexamine this group as it may inform about the evolutionary processes underlying the diversification of both non-pathogenic and pathogenic Cryptococcus lineages. Using genomic data, we reappraised the phylogenetic relationship of the four available strains and confirmed the genetic separation of C. amylolentus and T. wingfieldii (now Cryptococcus wingfieldii), and revealed an additional cryptic species, for which the name Cryptococcus floricola is proposed. Comparison of full-length chromosome assemblies revealed approximately 6% pairwise sequence divergence between the three species, and identified significant genomic changes, including inversions as well as a reciprocal translocation that involved inter-centromeric ectopic recombination, which together likely impose significant barriers to genetic exchange. Using genetic crosses, we show that while C. wingfieldii cannot interbreed with any of the other strains, C. floricola can undergo sexual reproduction with C. amylolentus. However, most of the spores resulting from this cross were inviable, and many were sterile, indicating that the two species are genetically isolated through intrinsic post-zygotic barriers and possibly due to niche differentiation. Genome sequencing and analysis of the progeny demonstrated decreased recombination frequency during meiosis in heterospecific crosses compared to C. amylolentus conspecific crosses. This study advances our understanding of speciation in fungi and highlights the power of genomics in assisting our ability to correctly identify and discriminate fungal species.Author SummaryThe idea of species as discrete natural units seems rather intuitive for most people, just as cells are the basic units of life. However, when observing variation across a species range, boundaries can become blurred making it less than obvious when different populations evolve into separate species. Additionally, separate species can still interbreed, such as lions breeding with tigers to produce a liger or a tigon (depending on the paternal and maternal species of origin), but the resulting offspring is usually inviable or sterile, which in turn is evidence that the parents involved are distinct species. Therefore, what species are and how they originate is still an open question in evolutionary biology. While recent advances have been made in the fields of animal and plant speciation, many other important components of biological diversity, such as fungi, are still understudied. Genome sequencing is now providing new tools to address the genetic mechanisms that drive divergence and reproductive isolation between populations, including genetic incompatibilities, sequence divergence, and chromosomal rearrangements. Here we focus on the Cryptococcus amylolentus species complex, a non-pathogenic fungal lineage closely related to the human pathogenic Cryptococcus neoformans/Cryptococcus gattii complex. Using genetic and genomic analysis we reexamined the species boundaries of four available isolates within the C. amylolentus complex and revealed three genetically isolated species. The genomes of these species are ~6% divergent and exhibit chromosome rearrangements, including translocations and small-scale inversions. Although two of the species (C. amylolentus and newly described C. floricola) are still able to interbreed, the resulting hybrid progeny were mostly inviable, and many were sterile, indicating that barriers to reproduction have already been established. Our results will foster additional studies addressing the transitions between non-pathogenic and pathogenic Cryptococcus lineages.

scholarly journals Genetic and Genomic Analyses Reveal Boundaries between Species Closely Related to Cryptococcus Pathogens

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Andrew Ryan Passer ◽  
Marco A. Coelho ◽  
Robert Blake Billmyre ◽  
Minou Nowrousian ◽  
Moritz Mittelbach ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Species Complex ◽  
Chromosomal Rearrangements ◽  
Fungal Species ◽  
Cryptococcus Gattii ◽  
Species Boundaries ◽  
Small Scale ◽  
Content Type ◽  
Fungal Lineage ◽  
Genomic Analyses

ABSTRACT Speciation is a central mechanism of biological diversification. While speciation is well studied in plants and animals, in comparison, relatively little is known about speciation in fungi. One fungal model is the Cryptococcus genus, which is best known for the pathogenic Cryptococcus neoformans/Cryptococcus gattii species complex that causes >200,000 new human infections annually. Elucidation of how these species evolved into important human-pathogenic species remains challenging and can be advanced by studying the most closely related nonpathogenic species, Cryptococcus amylolentus and Tsuchiyaea wingfieldii. However, these species have only four known isolates, and available data were insufficient to determine species boundaries within this group. By analyzing full-length chromosome assemblies, we reappraised the phylogenetic relationships of the four available strains, confirmed the genetic separation of C. amylolentus and T. wingfieldii (now Cryptococcus wingfieldii), and revealed an additional cryptic species, for which the name Cryptococcus floricola is proposed. The genomes of the three species are ∼6% divergent and exhibit significant chromosomal rearrangements, including inversions and a reciprocal translocation that involved intercentromeric ectopic recombination, which together likely impose significant barriers to genetic exchange. Using genetic crosses, we show that while C. wingfieldii cannot interbreed with any of the other strains, C. floricola can still undergo sexual reproduction with C. amylolentus. However, most of the resulting spores were inviable or sterile or showed reduced recombination during meiosis, indicating that intrinsic postzygotic barriers had been established. Our study and genomic data will foster additional studies addressing fungal speciation and transitions between nonpathogenic and pathogenic Cryptococcus lineages. IMPORTANCE The evolutionary drivers of speciation are critical to our understanding of how new pathogens arise from nonpathogenic lineages and adapt to new environments. Here we focus on the Cryptococcus amylolentus species complex, a nonpathogenic fungal lineage closely related to the human-pathogenic Cryptococcus neoformans/Cryptococcus gattii complex. Using genetic and genomic analyses, we reexamined the species boundaries of four available isolates within the C. amylolentus complex and revealed three genetically isolated species. Their genomes are ∼6% divergent and exhibit chromosome rearrangements, including translocations and small-scale inversions. Although two of the species (C. amylolentus and newly described C. floricola) were still able to interbreed, the resulting hybrid progeny were usually inviable or sterile, indicating that barriers to reproduction had already been established. These results advance our understanding of speciation in fungi and highlight the power of genomics in assisting our ability to correctly identify and discriminate fungal species.

scholarly journals Transfer of Meiothermus chliarophilus (Tenreiro et al.1995) Nobre et al. 1996, Meiothermus roseus Ming et al. 2016, Meiothermus terrae Yu et al. 2014 and Meiothermus timidus Pires et al. 2005, to Calidithermus gen. nov., as Calidithermus chliarophilus comb. nov., Calidithermus roseus comb. nov., Calidithermus terrae comb. nov. and Calidithermus timidus comb. nov., respectively, and emended description of the genus Meiothermus

2019 ◽  
Vol 69 (4) ◽  
pp. 1060-1069 ◽  
Author(s):  
Pedro Raposo ◽  
Tomeu Viver ◽  
Luciana Albuquerque ◽  
Hugo Froufe ◽  
Cristina Barroso ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Housekeeping Genes ◽  
Amino Acid Identity ◽  
Rrna Gene ◽  
Content Type ◽  
Link Type ◽  
As Species ◽  
Genotypic Characteristics ◽  
The 16S Rrna Gene ◽  
Core Genes

Chemotaxonomic parameters, phylogenetic analysis of the 16S rRNA gene, phylogenetic analysis of 90 housekeeping genes and 855 core genes, amino acid identity (AAI), average nucleotide identity (ANI) and genomic characteristics were used to examine the 13 species of the genus Meiothermus with validly published names to reclassify this genus. The results indicate that the species of the genus Meiothermus can be divided into three lineages on the basis of the results of the phylogenetic analysis, AAI, the guanine+cytosine (G+C) mole ratio, the ability to synthesize the red-pigmented carotenoid canthaxanthin and the colony colour, as well as other genomic characteristics. The results presented in this study circumscribe the genus Meiothermus to the species Meithermus ruber, Meiothermus cateniformans, Meiothermus taiwanensis, Meiothermus cerbereus, Meiothermus hypogaeus, Meiothermus luteus, Meiothermus rufus and Meiothermus granaticius, for which it is necessary to emend the genus Meiothermus . The species Meiothermus silvanus, which clearly represents a separate genus level lineage was not reclassified in this study for lack of any distinctive phenotypic or genotypic characteristics. The results of this study led us to reclassify the species Meiothermus chliarophilus, Meiothermus timidus, Meiothermus roseus and Meiothermus terrae as species of a novel genus for which we propose the epithet Calidithermus gen. nov.

scholarly journals Cryptococcus neoformans-Cryptococcus gattii Species Complex: an International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Amphotericin B and Flucytosine

2012 ◽  
Vol 56 (6) ◽  
pp. 3107-3113 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chowdhary ◽  
M. Cuenca-Estrella ◽  
A. Fothergill ◽  
J. Fuller ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Species Complex ◽  
Acquired Resistance ◽  
International Study ◽  
Resistance Mechanisms ◽  
Cryptococcus Gattii ◽  
Wild Type ◽  
Content Type ◽  
Cutoff Values

ABSTRACTClinical breakpoints (CBPs) are not available for theCryptococcus neoformans-Cryptococcus gattiispecies complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) forC. neoformansandC. gattiiversus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs forC. neoformans(including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs forC. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs forC. neoformanswere evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 μg/ml forC. neoformansVNI (97.2%) andC. gattiiVGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml forC. neoformans(98.5%) andC. gattiinontyped (100%) and VGII (99.2%) isolates; for flucytosine, 4 μg/ml forC. gattiinontyped (96.4%) and VGI (95.7%) isolates, 8 μg/ml for VNI (96.6%) isolates, and 16 μg/ml forC. neoformansnontyped (98.6%) andC. gattiiVGII (97.1%) isolates. Other molecular types had apparent variations in MIC distributions, but the number of laboratories contributing data was too low to allow us to ascertain that the differences were due to factors other than assay variation. ECVs may aid in the detection of isolates with acquired resistance mechanisms.

scholarly journals Protection of Mice against Experimental Cryptococcosis by Synthesized Peptides Delivered in Glucan Particles

mBio ◽  
2022 ◽  
Author(s):  
Charles A. Specht ◽  
E. Jane Homan ◽  
Chrono K. Lee ◽  
Zhongming Mou ◽  
Christina L. Gomez ◽  
...  
Keyword(s):  
Public Health ◽  
Cryptococcus Neoformans ◽  
Species Complex ◽  
Morbidity And Mortality ◽  
Content Type ◽  
Public Health Priority ◽  
Health Priority ◽  
Experimental Cryptococcosis ◽  
Human Use ◽  
Substantial Morbidity

Cryptococcosis, due to infection by fungi of the Cryptococcus neoformans species complex, is responsible for substantial morbidity and mortality in immunocompromised persons, particularly those with AIDS. Cryptococcal vaccines are a public health priority yet are not available for human use.

scholarly journals Continental Drift and Speciation of the Cryptococcus neoformans and Cryptococcus gattii Species Complexes

mSphere ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Arturo Casadevall ◽  
Joudeh B. Freij ◽  
Christopher Hann-Soden ◽  
John Taylor
Keyword(s):  
South America ◽  
Cryptococcus Neoformans ◽  
Species Complex ◽  
Continental Drift ◽  
Pathogenic Fungi ◽  
Cryptococcus Gattii ◽  
Evolutionary Divergence ◽  
Temporal Separation ◽  
Content Type ◽  
Species Complexes

ABSTRACT Genomic analysis has placed the origins of two human-pathogenic fungi, the Cryptococcus gattii species complex and the Cryptococcus neoformans species complex, in South America and Africa, respectively. Molecular clock calculations suggest that the two species separated ~80 to 100 million years ago. This time closely approximates the breakup of the supercontinent Pangea, which gave rise to South America and Africa. On the basis of the geographic distribution of these two species complexes and the coincidence of the evolutionary divergence and Pangea breakup times, we propose that a spatial separation caused by continental drift resulted in the emergence of the C. gattii and C. neoformans species complexes from a Pangean ancestor. We note that, despite the spatial and temporal separation that occurred approximately 100 million years ago, these two species complexes are morphologically similar, share virulence factors, and cause very similar diseases. Continuation of these phenotypic characteristics despite ancient separation suggests the maintenance of similar selection pressures throughout geologic ages.

scholarly journals Cryptococcus neoformans-Cryptococcus gattii Species Complex: an International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Fluconazole, Itraconazole, Posaconazole, and Voriconazole

2012 ◽  
Vol 56 (11) ◽  
pp. 5898-5906 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. I. Aller ◽  
E. Canton ◽  
L. R. Castañón-Olivares ◽  
A. Chowdhary ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Species Complex ◽  
Acquired Resistance ◽  
Cryptococcus Gattii ◽  
Yeast Nitrogen Base ◽  
Wild Type ◽  
Nitrogen Base ◽  
Content Type ◽  
Rpmi Medium ◽  
Cutoff Values

ABSTRACTEpidemiological cutoff values (ECVs) for theCryptococcus neoformans-Cryptococcus gattiispecies complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs forC. neoformans(including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs forC. gattii(including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium forC. neoformanswere evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 μg/ml (VNI,C. gattiinontyped, VGI, VGIIa, and VGIII), 16 μg/ml (C. neoformansnontyped, VNIII, and VGIV), and 32 μg/ml (VGII); itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml (C. neoformansandC. gattiinontyped and VGI to VGIII), and 1 μg/ml (VGIV); posaconazole, 0.25 μg/ml (C. neoformansnontyped and VNI) and 0.5 μg/ml (C. gattiinontyped and VGI); and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml (C. neoformansandC. gattiinontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 μg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.

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