Comparative Analysis of Environmental and Clinical Populations of<i>Cryptococcus neoformans</i>

Litvintseva, Anastasia P.; Kestenbaum, Lori A.; Vilgalys, Rytas; Mitchell, Thomas G.

doi:10.1128/jcm.43.2.556-564.2005

Cited by 133 publications

(165 citation statements)

References 43 publications

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“…The remaining 92 were MATa and were from different parts of the world, including Botswana. As expected, the Botswana population that contained strains of both mating types showed evidence of recombination and sexual reproduction (Litvintseva et al, 2003(Litvintseva et al, , 2006. In contrast, the remaining geographical populations that contained only MATa strains were largely clonal, with no clear evidence of recombination.…”

Section: Introductionmentioning

confidence: 74%

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Long-distance dispersal and recombination in environmental populations of Cryptococcus neoformans var. grubii from India

et al. 2008

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The basidiomycete yeast Cryptococcus neoformans is a cause of significant morbidity and mortality in immunocompromised hosts throughout the world. The sporadic nature of the infection and the limited empirical evidence for direct human-to-human transmission have led to the belief that infections in humans are predominantly caused by the inhalation of basidiospores from environmental sources. Therefore, analysing the structure of environmental populations of C. neoformans can significantly increase our understanding of its ecology, evolution and epidemiology. Decaying wood is a rich source of organic and inorganic compounds and is known to be a suitable ecological niche for many micro-organisms, including C. neoformans. However, relatively little is known about the population structure of C. neoformans sampled from decaying wood. In this study, we analysed samples of C. neoformans var. grubii colonizing decaying wood in tree hollows of nine tree species in five geographical locations (Delhi, Bulandshahar, Hathras, Amritsar and Amrouli) in north-western India. Multilocus sequence typing was conducted using five gene fragments for each of 78 isolates. All isolates belonged to mating type a. Population-genetic analyses identified no evidence for significant differentiation among populations belonging to either different geographical areas or different host tree species. Interestingly, despite the lack of mating type a strains in our survey, we found unambiguous evidence for recombination in our population analyses. Our results are consistent with the hypothesis of long-distance dispersal and recombination in environmental populations of this species in India.

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Section: Introductionmentioning

confidence: 74%

“…For example, an MLST study of the population structure of C. neoformans var. grubii involving 102 representative strains from different parts of the world showed that the global population contained three genetically distinct subgroups (Litvintseva et al, 2006). Ten of the 102 strains were MATa and they were all from Botswana.…”

Section: Introductionmentioning

confidence: 99%

Long-distance dispersal and recombination in environmental populations of Cryptococcus neoformans var. grubii from India

et al. 2008

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“…Although the results obtained have been variable, most authors have suggested that persistence or recurrence of the infection might be caused by relapse rather than reinfection and/or micro-evolution of the original isolate (Jain et al, 2005;Litvintseva et al, 2005). A multi-strain infection was rarely considered until a recent Fig.…”

Section: Discussionmentioning

confidence: 99%

Cryptococcus neoformans isolates from Yaoundé human immunodeficiency virus-infected patients exhibited intra-individual genetic diversity and variation in antifungal susceptibility profiles between isolates from the same patient

Ngouana

Drakulovski

Krasteva

et al. 2016

Journal of Medical Microbiology

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Cryptococcal meningitis is a dreadful opportunistic fungal infection amongst human immunodeficiency virus (HIV)-infected patients. One complication in the management of the disease is the possible infection of a patient by two or more different strains of Cryptococcus neoformans. This study investigated the intra-individual genetic diversity and antifungal susceptibility of C. neoformans isolates from Yaounde (Cameroon) HIV-infected patients with cryptococcal meningitis. Twenty-five clinical isolates were obtained during a prospective study. Five colonies were randomly collected from each initial sample. The 150 isolates obtained (125 colonies and 25 initial samples) were submitted to serotyping by multiplex PCR. Genotyping analyses were achieved using RFLP, and minisatellite-and microsatellite-length polymorphism. The antifungal susceptibility testing was carried out using a Sensititre YeastOne kit. Seven antifungals were tested: itraconazole, fluconazole, amphotericin B, ketoconazole, 5-fluorocytosine, posaconazole and voriconazole. The 150 isolates were identified as C. neoformans serotype A and genotype VNI. The microsatellite and minisatellite sequence analyses generated 15 genotypes. Six out of 25 (24 %) patients were found to be infected by two different genotypes. Antifungal susceptibility showed several profiles: posaconazole (0.015-0.25 µg ml À1 ), amphotericin B (0.06-1 µg ml À1 ), fluconazole (0.5-16 µg ml À1 ), itraconazole (0.008-0.12 µg ml À1 ), ketoconazole (0.008-0.12 µg ml À1 ), 5-fluorocytosine (0.25-16 µg ml À1 ) and voriconazole (0.008-0.12 µg ml À1 ). It was noted that isolates from the same patient might present different susceptibility profiles to an antifungal drug with differences of more than four dilutions. The results achieved highlighted the possible presence of isolates with different genotypes in a patient with dissimilar antifungal susceptibility profiles during a single episode of cryptococcal meningitis.

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“…Despite a long-recognized laboratory a-a sexual cycle, an overwhelming number of environmental and clinical isolates are of just one mating type, MATa (Kwon-Chung and Bennett 1978; Halliday et al 1999). In many pathogenic fungi, including C. neoformans, the population is largely clonal, yet these organisms maintain their ability to undergo both bisexual and unisexual reproduction (Litvintseva et al 2003(Litvintseva et al , 2005. In particular, clinical isolates of C. neoformans often are derived from large clonal populations of environmental isolates that show evidence of recombination, despite the paucity of MATa isolates in some sampled populations.…”

Section: Discussionmentioning

confidence: 99%

“…Extensive sampling of C. neoformans populations revealed .99% of cells are MATa (Lengeler et al 2000;Litvintseva et al 2003Litvintseva et al , 2005Heitman 2010). The preponderance of MATa cells raises the question of how frequently C. neoformans undergoes sexual reproduction in natural populations.…”

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confidence: 99%

Unisexual Reproduction Reverses Muller’s Ratchet

Roach¹,

Heitman

2014

Genetics

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Cryptococcus neoformans is a pathogenic basidiomycetous fungus that engages in outcrossing, inbreeding, and selfing forms of unisexual reproduction as well as canonical sexual reproduction between opposite mating types. Long thought to be clonal, .99% of sampled environmental and clinical isolates of C. neoformans are MATa, limiting the frequency of opposite mating-type sexual reproduction. Sexual reproduction allows eukaryotic organisms to exchange genetic information and shuffle their genomes to avoid the irreversible accumulation of deleterious changes that occur in asexual populations, known as Muller's ratchet. We tested whether unisexual reproduction, which dispenses with the requirement for an opposite mating-type partner, is able to purge the genome of deleterious mutations. We report that the unisexual cycle can restore mutant strains of C. neoformans to wild-type genotype and phenotype, including prototrophy and growth rate. Furthermore, the unisexual cycle allows attenuated strains to purge deleterious mutations and produce progeny that are returned to wild-type virulence. Our results show that unisexual populations of C. neoformans are able to avoid Muller's ratchet and loss of fitness through a unisexual reproduction cycle involving a-a cell fusion, nuclear fusion, and meiosis. Similar types of unisexual reproduction may operate in other pathogenic and saprobic eukaryotic taxa.

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Comparative Analysis of Environmental and Clinical Populations ofCryptococcus neoformans

Cited by 133 publications

References 43 publications

Long-distance dispersal and recombination in environmental populations of Cryptococcus neoformans var. grubii from India

Long-distance dispersal and recombination in environmental populations of Cryptococcus neoformans var. grubii from India

Cryptococcus neoformans isolates from Yaoundé human immunodeficiency virus-infected patients exhibited intra-individual genetic diversity and variation in antifungal susceptibility profiles between isolates from the same patient

Unisexual Reproduction Reverses Muller’s Ratchet

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