Molecular Markers Reveal Epidemiological Patterns and Evolutionary Histories of the Human Pathogenic Cryptococcus

Hong, Nan; Chen, Min; Xu, Jianping

doi:10.3389/fcimb.2021.683670

Cited by 20 publications

(21 citation statements)

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“…Over the past four decades, a variety of genetic markers have been used to analyze strains and populations of human pathogenic fungi ( Hong et al., 2021 ), including for C. tropicalis (e.g., Tavanti et al., 2005 ; O’Brien et al., 2021 ). Most of these genetic markers are based on variations in DNA sequences.…”

Section: Evidence For Clonality and Recombination In Natural C Tropicalis Populationsmentioning

confidence: 99%

Is Natural Population of Candida tropicalis Sexual, Parasexual, and/or Asexual?

2021

Front. Cell. Infect. Microbiol.

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Candida tropicalis is one of the most common opportunistic yeast pathogens of humans, especially prevalent in tropical and subtropical regions. This yeast has broad ecological distributions, can be found in both terrestrial and aquatic ecosystems, including being associated with a diversity of trees, animals, and humans. Evolutionary theory predicts that organisms thriving in diverse ecological niches likely have efficient mechanisms to generate genetic diversity in nature. Indeed, abundant genetic variations have been reported in natural populations (both environmental and clinical) of C. tropicalis. However, at present, our understanding on how genetic diversity is generated in natural C. tropicalis population remains controversial. In this paper, I review the current understanding on the potential modes of reproduction in C. tropicalis. I describe expectations of the three modes of reproduction (sexual, parasexual, and asexual) and compare them with the observed genotypic variations in natural populations. Though sexual and parasexual reproduction cannot be excluded, the analyses suggest asexual reproduction alone could explain all the observations reported so far. The results here have implications for understanding the evolution and epidemiology of C. tropicalis and other related human fungal pathogens.

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Section: Evidence For Clonality and Recombination In Natural C Tropicalis Populationsmentioning

confidence: 99%

Is Natural Population of Candida tropicalis Sexual, Parasexual, and/or Asexual?

2021

Front. Cell. Infect. Microbiol.

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“…Notably, antifungal susceptibility, particularly to fluconazole and 5-fluorocytosine, has been noted to vary in correlation not only with molecular types but also with HIV status ( Espinel-Ingroff et al, 2012 ; Li et al, 2012 ; Arsic Arsenijevic et al, 2014 ). To investigate the molecular epidemiology of local cryptococcal isolates, several molecular typing methods have been developed, for example, PCR-fingerprinting, randomly amplified polymorphic DNA (RAPD), PCR-restriction fragment length polymorphism (PCR-RFLP), amplified fragment length polymorphism (AFLP), microsatellite typing, multilocus microsatellite typing (MLMT), multilocus sequence typing (MLST), and whole-genome sequencing (WGS) ( Bovers et al, 2008 ; Meyer et al, 2009 ; Li et al, 2013 ; Hong et al, 2021 ). Extensive studies have recommended MLST as the preferred method among these molecular techniques because of its excellent discrimination ability and reproducibility between different laboratories.…”

Section: Introductionmentioning

confidence: 99%

Molecular Epidemiology and Antifungal Resistance of Cryptococcus neoformans From Human Immunodeficiency Virus-Negative and Human Immunodeficiency Virus-Positive Patients in Eastern China

Zhou

Zhu

et al. 2022

Front. Microbiol.

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Cryptococcosis is an opportunistic and potentially lethal infection caused by Cryptococcus neoformans and Cryptococcus gattii complex, which affects both immunocompromised and immunocompetent people, and it has become a major public health concern worldwide. In this study, we characterized the molecular epidemiology and antifungal susceptibility of 133 C. neoformans isolates from East China Invasive Fungal Infection Group (ECIFIG), 2017–2020. Isolates were identified to species level by matrix-assisted laser desorption ionization-time of flight mass spectrometry and confirmed by IGS1 sequencing. Whole-genome sequencing (WGS) was conducted on three multidrug-resistant isolates. Among the 133 strains, 61 (45.86%) were isolated from HIV-positive patients and 72 (54.16%) were isolated from HIV-negative patients. In total, C. neoformans var. grubii accounted for 97.74% (130/133), while C. neoformans var. neoformans was rare (2.06%, 3/133). The strains were further classified into nine sequence types (STs) dominated by ST5 (90.23%, 120/133) with low genetic diversity. No association was observed between STs and HIV status. All strains were wild type to voriconazole, while high antifungal minimal inhibitory concentrations (MICs) above the epidemiological cutoff values (ECVs) were observed in C. neoformans strains, and more than half of isolates were non-wild-type to amphotericin B (89.15%, 109/133). Eight isolates were resistant to fluconazole, and eight isolates were non-wild type to 5-fluorocytosine. Furthermore, WGS has verified the novel mutations of FUR1 in 5-fluorocytosine-resistant strains. In one isolate, aneuploidy of chromosome 1 with G484S mutation of ERG11 was observed, inducing high-level resistance (MIC: 32 μg/ml) to fluconazole. In general, our data showed that there was no significant difference between HIV-positive and HIV-negative patients on STs, and we elucidate the resistant mechanisms of C. neoformans from different perspectives. It is important for clinical therapy and drug usage in the future.

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“…CNSC is a highly heterogeneous group of organisms, with divergent lineages showing >10% nucleotide sequence divergence [ 1 ]. Over the last 50 years, a variety of molecular markers have been used to identify strains of CNSC [ 8 ]. These markers have revealed divergent lineages within CNSC.…”

Section: Introductionmentioning

confidence: 99%

“…C. neoformans (Serotype A) is further divided into three major molecular types, VNI, VNB and VNII, while C. deneoformans (serotype D) corresponds to the molecular type VNIV. In addition to these four major molecular types, VNB was further divided into two subtypes, VNBI and VNBII, and diploid/aneuploid hybrids have been observed in nature and are referred to as VNIII or serotype AD hybrids [ 1 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Analyses of the Global Multilocus Genotypes of the Human Pathogenic Yeast Cryptococcus neoformans Species Complex

Hitchcock

2022

Genes

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Cryptococcus neoformans species complex (CNSC) is a globally distributed human opportunistic yeast pathogen consisting of five major molecular types (VNI, VNII, VNB, VNIII and VNIV) belonging to two species, C. neoformans (VNI, VNII and VNB, collectively called serotype A) and C. deneoformans (VNIV, commonly called serotype D), and their hybrids (VNIII, serotype AD). Over the years, many studies have analyzed the geographical distribution and genetic diversity of CNSC. However, the global population structure and mode of reproduction remain incompletely described. In this study, we analyze the published multilocus sequence data at seven loci for CNSC. The combined sequences at the seven loci identified a total of 657 multilocus sequence types (STs), including 296 STs with known geographic information, representing 4200 non-redundant isolates from 31 countries and four continents. Among the 296 STs, 78 and 52 were shared among countries and continents, respectively, representing 3643 of the 4200 isolates. Except for the clone-corrected serotype D sample among countries, our analysis of the molecular variance of the 4200 isolates revealed significant genetic differentiations among countries and continents in populations of CNSC, serotype A, and serotype D. Phylogenetic analyses of the concatenated sequences of all 657 STs revealed several large clusters corresponding to the major molecular types. However, several rare but distinct STs were also found, representing potentially novel molecular types and/or hybrids of existing molecular types. Phylogenetic incompatibility analyses revealed evidence for recombination within all four major molecular types—VNI, VNII, VNIV and VNB—as well as within two VNB subclades, VNBI and VNBII, and two ST clusters around the most common STs, ST5 and ST93. However, linkage disequilibrium analyses rejected the hypothesis of random recombination across most samples. Together, our results suggest evidence for historical differentiation, frequent recent gene flow, clonal expansion and recombination within and between lineages of the global CNSC population.

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Molecular Markers Reveal Epidemiological Patterns and Evolutionary Histories of the Human Pathogenic Cryptococcus

Cited by 20 publications

References 159 publications

Is Natural Population of Candida tropicalis Sexual, Parasexual, and/or Asexual?

Is Natural Population of Candida tropicalis Sexual, Parasexual, and/or Asexual?

Molecular Epidemiology and Antifungal Resistance of Cryptococcus neoformans From Human Immunodeficiency Virus-Negative and Human Immunodeficiency Virus-Positive Patients in Eastern China

Analyses of the Global Multilocus Genotypes of the Human Pathogenic Yeast Cryptococcus neoformans Species Complex

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