Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals

Byrnes, Edmond J.; Bartlett, Karen H.; Perfect, John R.; Heitman, Joseph

doi:10.1016/j.micinf.2011.05.009

Cited by 138 publications

(138 citation statements)

References 120 publications

(223 reference statements)

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“…C. neoformans var. grubii is responsible of almost all the infections in AIDS patients whilst C. gattii affects mainly apparently immunocompetent persons (6). Both C. neoformans and C. gattii invade essentially the cerebral parenchyma; however, C. gattii is more likely to produce pulmonary and cerebral masses (cryptococcomas) (6).…”

mentioning

confidence: 99%

“…grubii is responsible of almost all the infections in AIDS patients whilst C. gattii affects mainly apparently immunocompetent persons (6). Both C. neoformans and C. gattii invade essentially the cerebral parenchyma; however, C. gattii is more likely to produce pulmonary and cerebral masses (cryptococcomas) (6). conditions, infections caused by the members of the C. neoformans complex have become important causes of morbid-mortality with approximately 5-10% of the patients with CD4+ lymphopenia developing cryptococcosis (7).…”

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confidence: 99%

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Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

et al. 2012

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Introduction: A survey on cryptococcosis is being conducted regularly in Colombia since 1997. We present hereby the results corresponding to patients diagnosed from 2006 to 2010. Objective: To analyze the data obtained during this period. Materials and methods:Retrospective analysis of the corresponding surveys. Results: A total of 526 surveys originating from 72% of the Colombian political divisions were received during the 5-year period. Most patients (76.6%) were males and 74.9% were 21-50 years old. The most prevalent risk factor was HIV infection (83.5%) with cryptococcosis defining AIDS in 23% of the cases. In the general population the estimated mean annual incidence rate for cryptococcosis was 2.4 x 10 6 inhabitants while in AIDS patients this rate rose to 3.3 x 10 3 . In 474 surveys stating clinical features, most frequent complaints were headache 84.5%, fever 63.4%, nausea and vomiting 57.5%, mental alterations 46.3%, meningeal signs 33.0%, cough 26.4% and visual alterations 24.5%. Neurocryptococcosis was recorded in 81.8% of the cases. Laboratory diagnosis was based on direct examination, culture and latex in 29.3% cases. From 413 Cryptococcus isolates analyzed, 95.6% were identified as C. neoformans var. grubii, 1% C. neoformans var. neoformans, and 3.4% C. gattii. Treatment was reported for 71.6% of the cases with amphotericin B alone or in combination with fluconazole prescribed in 28%. Conclusions: Surveys done through passive surveillance continue to be sentinel markers for HIV infection and represent a systematic approach to the study of opportunistic problems regularly afflicting AIDS patients since cryptococcosis requires no compulsory notification in Colombia. Author contributions:Patricia Escandón: played an important role in writing and preparing the manuscript, in charge of the surveillance at the Instituto Nacional de Salud, controlled receipt of questionnaires. Catalina de Bedout: in charge of the mycological diagnosis for all Corporación para Investigaciones Biológicas cases, established links with physicians in charge of patients, controlled receipt of questionnaires and performed the susceptibility testing in all isolates. Jairo Lizarazo: physician in charge of the patients from Norte de Santander, checked the questionnaire's contents for medical accuracy, analyzed the data through statistical analysis. Clara Inés Agudelo: worked all long in the surveillance study, played an important role in preparation of the manuscript and in the analysis of the data, including statistical tests. Ángela Tobón: examined many of the Corporación para Investigaciones Biológicas patients, filled in the corresponding questionnaires, supervised the clinical aspects of most patients and served as a consultant for other physicians in charge of cryptococcosis patients. Solmara Bello: in charge of the mycological diagnosis for Instituto Nacional de Salud cases. Ángela Restrepo: surveillance of the whole program, contacting physicians and serving as consultant for all participants, analyzing data, writing of ...

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Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

et al. 2012

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“…70 The ability of C. neoformans and C. gattii to grow at host body temperature (37 C) is one of the virulence attributes that is controlled by the calcineurin signaling pathway. 40,43 In addition, calcineurin is also required for growth at alkaline pH, hyphal elongation during mating and monokaryotic fruiting.…”

Section: Candida Cryptococcus and Emerging Moldsmentioning

confidence: 99%

Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach

et al. 2016

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Increases in the incidence and mortality due to the major invasive fungal infections such as aspergillosis, candidiasis and cryptococcosis caused by the species of Aspergillus, Candida and Cryptococcus, are a growing threat to the immunosuppressed patient population. In addition to the limited armamentarium of the current classes of antifungal agents available (pyrimidine analogs, polyenes, azoles, and echinocandins), their toxicity, efficacy and the emergence of resistance are major bottlenecks limiting successful patient outcomes. Although these drugs target distinct fungal pathways, there is an urgent need to develop new antifungals that are more efficacious, fungalspecific, with reduced or no toxicity and simultaneously do not induce resistance. Here we review several lines of evidence which indicate that the calcineurin signaling pathway, a target of the immunosuppressive drugs FK506 and cyclosporine A, orchestrates growth, virulence and drug resistance in a variety of fungal pathogens and can be exploited for novel antifungal drug development.

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“…Recent evidence has suggested that unisexual reproduction and recombination play an important role in generating virulent strains of Cryptococcus and other eukaryotic pathogens, including both fungi and parasites (Jenni et al 1986;Gaunt et al 2003;Fraser et al 2005;Akopyants et al 2009;Byrnes et al 2010Byrnes et al , 2011Wendte et al 2010;Minot et al 2012;Inbar et al 2013;Voelz et al 2013;Billmyre et al 2014). We tested whether parental strains with mutations that compromise virulence are able to undergo unisexual reproduction to produce virulent progeny.…”

Section: Unisexual Reproduction Between Attenuated Strains Restores Tmentioning

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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Cryptococcus gattii: an emerging fungal pathogen infecting humans and animals

Cited by 138 publications

References 120 publications

Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

Criptococosis en Colombia: resultados de la encuesta nacional, 2006-2010

Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach

Unisexual Reproduction Reverses Muller’s Ratchet

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