A Landscape of the Genomic Structure of Cryptococcus neoformans in Colombian Isolates

Cryptococcus neoformans species complexes are recognized as environmental fungi responsible for lethal meningoencephalitis in immunocompromised individuals. Despite the vast knowledge about the epidemiology and genetic diversity of this fungus in different regions of the world, more studies are necessary to comprehend the genomic profiles across South America, including Colombia, considered to be the second country with the highest number of Cryptococcosis. Here, we sequenced and analyzed the genomic architecture of 29 Colombian C. neoformans isolates and evaluated the phylogenetic relationship of these strains with publicly available C. neoformans genomes. The phylogenomic analysis showed that 97% of the isolates belonged to the VNI molecular type and the presence of sub-lineages and sub-clades. We evidenced a karyotype without changes, a low number of genes with copy number variations, and a moderate number of single-nucleotide polymorphisms (SNPs). Additionally, a difference in the number of SNPs between the sub-lineages/sub-clades was observed; some were involved in crucial fungi biological processes. Our study demonstrated the intraspecific divergence of C. neoformans in Colombia. These findings provide evidence that Colombian C. neoformans isolates do not probably require significant structural changes as adaptation mechanisms to the host. To the best of our knowledge, this is the first study to report the whole genome sequence of Colombian C. neoformans isolates.

[1]  J. Beardsley,et al.  What’s New in Cryptococcus gattii: From Bench to Bedside and Beyond , 2022, Journal of fungi.

[2]  Xudong Zhu,et al.  The RNA Helicase Ski2 in the Fungal Pathogen Cryptococcus neoformans Highlights Key Roles in Azoles Resistance and Stress Tolerance. , 2022, Medical mycology.

[3]  M. Muñoz,et al.  Deciphering the Association among Pathogenicity, Production and Polymorphisms of Capsule/Melanin in Clinical Isolates of Cryptococcus neoformans var. grubii VNI , 2022, Journal of fungi.

[4]  N. Wiederhold.  Emerging Fungal Infections: New Species, New Names, and Antifungal Resistance , 2021, Clinical chemistry.

[5]  Ursula Oggenfuss,et al.  The population genetics of adaptation through copy-number variation in a fungal plant pathogen , 2021, bioRxiv.

[6]  Christina A. Cuomo,et al.  Gene Expression of Diverse Cryptococcus Isolates during Infection of the Human Central Nervous System , 2021, mBio.

[7]  C. Muskus,et al.  Revisiting the heterogeneous global genomic population structure of Leishmania infantum , 2021, Microbial genomics.

[8]  Kirsten Nielsen,et al.  The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G2 Arrest in Cryptococcus , 2021, bioRxiv.

[9]  M. Fisher,et al.  The need for environmental surveillance to understand the ecology, epidemiology and impact of Cryptococcus infection in Africa , 2021, FEMS microbiology ecology.

[10]  Z. Sánchez-Quitian,et al.  Environmental Status of Cryptococcus neoformans and Cryptococcus gattii in Colombia , 2021, Journal of fungi.

[11]  Jianping Xu,et al.  Molecular Markers Reveal Epidemiological Patterns and Evolutionary Histories of the Human Pathogenic Cryptococcus , 2021, Frontiers in Cellular and Infection Microbiology.

[12]  N. van Rhijn,et al.  The Consequences of Our Changing Environment on Life Threatening and Debilitating Fungal Diseases in Humans , 2021, Journal of fungi.

[13]  N. E. Nnadi,et al.  Climate change and the emergence of fungal pathogens , 2021, PLoS pathogens.

[14]  W. Meyer,et al.  Cryptococcus neoformans and Cryptococcus gattii Species Complexes in Latin America: A Map of Molecular Types, Genotypic Diversity, and Antifungal Susceptibility as Reported by the Latin American Cryptococcal Study Group , 2021, Journal of fungi.

[15]  Rhys A. Farrer,et al.  Genomic epidemiology of a Cryptococcus neoformans case cluster in Glasgow, Scotland, 2018 , 2021, Microbial genomics.

[16]  Christina A. Cuomo,et al.  Application of an optimized annotation pipeline to the Cryptococcus deuterogattii genome reveals dynamic primary metabolic gene clusters and genomic impact of RNAi loss , 2020, bioRxiv.

[17]  Olga Chernomor,et al.  IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era , 2019, bioRxiv.

[18]  Christina A. Cuomo,et al.  A New Lineage of Cryptococcus gattii (VGV) Discovered in the Central Zambezian Miombo Woodlands , 2019, mBio.

[19]  G. Dougan,et al.  Three phylogenetic groups have driven the recent population expansion of Cryptococcus neoformans , 2019, Nature Communications.

[20]  P. Bork,et al.  Interactive Tree Of Life (iTOL) v4: recent updates and new developments , 2019, Nucleic Acids Res..

[21]  C. d’Enfert,et al.  Within-Host Genomic Diversity of Candida albicans in Healthy Carriers , 2019, Scientific Reports.

[22]  K. Kwon-Chung,et al.  Cryptococcus neoformans, Unlike Candida albicans, Forms Aneuploid Clones Directly from Uninucleated Cells under Fluconazole Stress , 2018, mBio.

[23]  R. Puccinelli,et al.  Diversification of DNA binding specificities enabled SREBP transcription regulators to expand the repertoire of cellular functions that they govern in fungi , 2018, PLoS genetics.

[24]  Jianping Xu,et al.  Hybrids and hybridization in the Cryptococcus neoformans and Cryptococcus gattii species complexes. , 2018, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[25]  P. Escandón,et al.  First isolation and molecular characterization of Cryptococcus neoformans var. grubii in excreta of birds in the urban perimeter of the Municipality of Popayán, Colombia. , 2018, Revista iberoamericana de micologia.

[26]  G. Sherlock,et al.  Gene flow contributes to diversification of the major fungal pathogen Candida albicans , 2018, Nature Communications.

[27]  M. Muñoz,et al.  Estimating the Intra-taxa Diversity, Population Genetic Structure, and Evolutionary Pathways of Cryptococcus neoformans and Cryptococcus gattii , 2018, Front. Genet..

[28]  Matthew Z. Anderson,et al.  Functional diversification accompanies gene family expansion of MED2 homologs in Candida albicans , 2018, PLoS genetics.

[29]  E. Castañeda,et al.  Cryptococcosis in Colombia: Compilation and Analysis of Data from Laboratory-Based Surveillance , 2018, Journal of fungi.

[30]  Christina A. Cuomo,et al.  Advances in Cryptococcus genomics: insights into the evolution of pathogenesis , 2018, Memorias do Instituto Oswaldo Cruz.

[31]  S. Leibundgut-Landmann,et al.  Modulation of the Fungal-Host Interaction by the Intra-Species Diversity of C. albicans , 2018, Pathogens.

[32]  Antonis Rokas,et al.  Copy Number Variation in Fungi and Its Implications for Wine Yeast Genetic Diversity and Adaptation , 2017, bioRxiv.

[33]  M. Castanheira,et al.  Monitoring Antifungal Resistance in a Global Collection of Invasive Yeasts and Molds: Application of CLSI Epidemiological Cutoff Values and Whole-Genome Sequencing Analysis for Detection of Azole Resistance in Candida albicans , 2017, Antimicrobial Agents and Chemotherapy.

[34]  D. Boulware,et al.  Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. , 2017, The Lancet. Infectious diseases.

[35]  Christina A. Cuomo,et al.  Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level , 2017, Genetics.

[36]  J. Heitman,et al.  Natural mismatch repair mutations mediate phenotypic diversity and drug resistance in Cryptococcus deuterogattii , 2017, bioRxiv.

[37]  G. Bussotti,et al.  Modulation of Aneuploidy in Leishmania donovani during Adaptation to Different In Vitro and In Vivo Environments and Its Impact on Gene Expression , 2017, mBio.

[38]  Christina A Cuomo,et al.  Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans , 2017, bioRxiv.

[39]  Christina A. Cuomo,et al.  Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii , 2017, mBio.

[40]  D. Engelthaler,et al.  MLST-Based Population Genetic Analysis in a Global Context Reveals Clonality amongst Cryptococcus neoformans var. grubii VNI Isolates from HIV Patients in Southeastern Brazil , 2017, PLoS neglected tropical diseases.

[41]  M. Fisher,et al.  Genomic epidemiology of Cryptococcus yeasts identifies adaptation to environmental niches underpinning infection across an African HIV/AIDS cohort , 2016, Molecular ecology.

[42]  M. Fisher,et al.  A Population Genomics Approach to Assessing the Genetic Basis of Within-Host Microevolution Underlying Recurrent Cryptococcal Meningitis Infection , 2016, G3: Genes, Genomes, Genetics.

[43]  D. Engelthaler,et al.  MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors , 2016, PLoS neglected tropical diseases.

[44]  H. Lumbsch,et al.  Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex. , 2015, Fungal genetics and biology : FG & B.

[45]  Phillip A. Richmond,et al.  Polyploidy can drive rapid adaptation in yeast , 2015, Nature.

[46]  Christina A. Cuomo,et al.  Highly Recombinant VGII Cryptococcus gattii Population Develops Clonal Outbreak Clusters through both Sexual Macroevolution and Asexual Microevolution , 2014, mBio.

[47]  T. Doering,et al.  Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. , 2014, Cold Spring Harbor perspectives in medicine.

[48]  J. Heitman,et al.  Cryptococcus gattii VGIII Isolates Causing Infections in HIV/AIDS Patients in Southern California: Identification of the Local Environmental Source as Arboreal , 2014, PLoS pathogens.

[49]  Jacqueline E. Schein,et al.  Analysis of the Genome and Transcriptome of Cryptococcus neoformans var. grubii Reveals Complex RNA Expression and Microevolution Leading to Virulence Attenuation , 2014, PLoS genetics.

[50]  T. Beilharz,et al.  Introns Regulate Gene Expression in Cryptococcus neoformans in a Pab2p Dependent Pathway , 2013, PLoS genetics.

[51]  J. Fraser,et al.  Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans , 2013, PloS one.

[52]  M. Cogliati.  Global Molecular Epidemiology of Cryptococcus neoformans and Cryptococcus gattii: An Atlas of the Molecular Types , 2013, Scientifica.

[53]  K. Kwon-Chung,et al.  Aneuploidy and Drug Resistance in Pathogenic Fungi , 2012, PLoS pathogens.

[54]  Pablo Cingolani,et al.  © 2012 Landes Bioscience. Do not distribute. , 2022 .

[55]  Matko Bosnjak,et al.  REVIGO Summarizes and Visualizes Long Lists of Gene Ontology Terms , 2011, PloS one.

[56]  Hiten D. Madhani,et al.  Systematic Genetic Analysis of Virulence in the Human Fungal Pathogen Cryptococcus neoformans , 2008, Cell.

[57]  T. Sorrell,et al.  Role and mechanism of phosphatidylinositol‐specific phospholipase C in survival and virulence of Cryptococcus neoformans , 2008, Molecular microbiology.

[58]  D. Kosman,et al.  Iron Source Preference and Regulation of Iron Uptake in Cryptococcus neoformans , 2008, PLoS pathogens.

[59]  Ping Wang,et al.  Role of Protein O-Mannosyltransferase Pmt4 in the Morphogenesis and Virulence of Cryptococcus neoformans , 2006, Eukaryotic Cell.

[60]  K. Lemmer,et al.  Molecular analysis of 311 Cryptococcus neoformans isolates from a 30-month ECMM survey of cryptococcosis in Europe. , 2006, FEMS yeast research.

[61]  B. Wickes,et al.  Genotyping of Turkish environmental Cryptococcus neoformans var. neoformans isolates by pulsed field gel electrophoresis and mating type , 2006, Mycoses.

[62]  D. Huson,et al.  Application of phylogenetic networks in evolutionary studies. , 2006, Molecular biology and evolution.

[63]  J. Heitman,et al.  Deciphering the Model Pathogenic Fungus Cryptococcus Neoformans , 2005, Nature Reviews Microbiology.

[64]  V. Prachayasittikul,et al.  Electrophoretic karyotypes of C. neoformans serotype A recovered from Thai Patients with AIDS , 2005, Mycopathologia.

[65]  J. Heitman,et al.  Cyclic AMP-Dependent Protein Kinase Catalytic Subunits Have Divergent Roles in Virulence Factor Production in Two Varieties of the Fungal Pathogen Cryptococcus neoformans , 2004, Eukaryotic Cell.

[66]  W. Meyer,et al.  Molecular Typing of IberoAmerican Cryptococcus neoformans Isolates , 2003, Emerging infectious diseases.

[67]  T. Kirchhausen,et al.  Three ways to make a vesicle , 2000, Nature Reviews Molecular Cell Biology.

[68]  Jinjiang Fan,et al.  Direct PCR of Cryptococcus neoformans MATα andMATa Pheromones To Determine Mating Type, Ploidy, and Variety: a Tool for Epidemiological and Molecular Pathogenesis Studies , 2000, Journal of Clinical Microbiology.