Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>

ABSTRACT Koch’s postulates are criteria establishing a causal relationship between a microbe and a disease that lead to the assumption that diseases are caused by a single strain or its evolved forms. Cryptococcus neoformans is a life-threatening human fungal pathogen responsible for an estimated 1...

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Autores principales:	Marie Desnos-Ollivier, Sweta Patel, Adam R. Spaulding, Caroline Charlier, Dea Garcia-Hermoso, Kirsten Nielsen, Françoise Dromer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c6a2378839c746d399e035702774b558
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spelling	oai:doaj.org-article:c6a2378839c746d399e035702774b5582021-11-15T15:38:13ZMixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>10.1128/mBio.00091-102150-7511https://doaj.org/article/c6a2378839c746d399e035702774b5582010-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00091-10https://doaj.org/toc/2150-7511ABSTRACT Koch’s postulates are criteria establishing a causal relationship between a microbe and a disease that lead to the assumption that diseases are caused by a single strain or its evolved forms. Cryptococcus neoformans is a life-threatening human fungal pathogen responsible for an estimated 1 million cases of cryptococcosis/year, predominantly meningoencephalitis. To assess the molecular diversity of clinical isolates and gain knowledge of C. neoformans biology in the host, we analyzed clinical cultures collected during the prospective CryptoA/D study. Using molecular analysis of unpurified isolates, we demonstrated that mixed infections in humans are more common than previously thought, occurring in almost 20% of patients diagnosed with cryptococcosis. These mixed infections are composed of different mating types, serotypes, and/or genotypes. We also identified genetically related haploid and diploid strains in the same patients. Experimental infections and quantitative PCR show that these ploidy changes can result from endoreplication (duplication of DNA content) and that shuttling between haploid and diploid states can occur, suggesting in vivo evolution. Thus, the concept of one strain/one infection does not hold true for C. neoformans and may apply to other environmentally acquired fungal pathogens. Furthermore, the possibility of mixed and/or evolving infections should be taken into account when developing therapeutic strategies against these pathogens. IMPORTANCECryptococcus neoformans is a life-threatening human fungal pathogen that is present in the environment and is responsible for an estimated 1 million cases of cryptococcosis/year, predominantly meningoencephalitis in HIV-infected patients. To assess the molecular diversity of clinical isolates and gain knowledge of C. neoformans biology in the host, we analyzed clinical cultures collected during a prospective study on cryptococcosis. Using molecular analysis of unpurified isolates, we uncovered an unexpectedly high frequency (almost 20%) of mixed infections. We further demonstrated that these mixed infections could result from infestation by multiple strains acquired from the environment. We also made the serendipitous discovery of in vivo evolution leading to endoreplication of the yeasts within the host. Thus, the concept of one strain causing one infection does not hold true for C. neoformans and potentially for other environmentally acquired fungal pathogens. The possibility of mixed and/or evolving infections should be taken into account when developing therapeutic strategies against these pathogens.Marie Desnos-OllivierSweta PatelAdam R. SpauldingCaroline CharlierDea Garcia-HermosoKirsten NielsenFrançoise DromerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 1 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Marie Desnos-Ollivier Sweta Patel Adam R. Spaulding Caroline Charlier Dea Garcia-Hermoso Kirsten Nielsen Françoise Dromer Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
description	ABSTRACT Koch’s postulates are criteria establishing a causal relationship between a microbe and a disease that lead to the assumption that diseases are caused by a single strain or its evolved forms. Cryptococcus neoformans is a life-threatening human fungal pathogen responsible for an estimated 1 million cases of cryptococcosis/year, predominantly meningoencephalitis. To assess the molecular diversity of clinical isolates and gain knowledge of C. neoformans biology in the host, we analyzed clinical cultures collected during the prospective CryptoA/D study. Using molecular analysis of unpurified isolates, we demonstrated that mixed infections in humans are more common than previously thought, occurring in almost 20% of patients diagnosed with cryptococcosis. These mixed infections are composed of different mating types, serotypes, and/or genotypes. We also identified genetically related haploid and diploid strains in the same patients. Experimental infections and quantitative PCR show that these ploidy changes can result from endoreplication (duplication of DNA content) and that shuttling between haploid and diploid states can occur, suggesting in vivo evolution. Thus, the concept of one strain/one infection does not hold true for C. neoformans and may apply to other environmentally acquired fungal pathogens. Furthermore, the possibility of mixed and/or evolving infections should be taken into account when developing therapeutic strategies against these pathogens. IMPORTANCECryptococcus neoformans is a life-threatening human fungal pathogen that is present in the environment and is responsible for an estimated 1 million cases of cryptococcosis/year, predominantly meningoencephalitis in HIV-infected patients. To assess the molecular diversity of clinical isolates and gain knowledge of C. neoformans biology in the host, we analyzed clinical cultures collected during a prospective study on cryptococcosis. Using molecular analysis of unpurified isolates, we uncovered an unexpectedly high frequency (almost 20%) of mixed infections. We further demonstrated that these mixed infections could result from infestation by multiple strains acquired from the environment. We also made the serendipitous discovery of in vivo evolution leading to endoreplication of the yeasts within the host. Thus, the concept of one strain causing one infection does not hold true for C. neoformans and potentially for other environmentally acquired fungal pathogens. The possibility of mixed and/or evolving infections should be taken into account when developing therapeutic strategies against these pathogens.
format	article
author	Marie Desnos-Ollivier Sweta Patel Adam R. Spaulding Caroline Charlier Dea Garcia-Hermoso Kirsten Nielsen Françoise Dromer
author_facet	Marie Desnos-Ollivier Sweta Patel Adam R. Spaulding Caroline Charlier Dea Garcia-Hermoso Kirsten Nielsen Françoise Dromer
author_sort	Marie Desnos-Ollivier
title	Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_short	Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_full	Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_fullStr	Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_full_unstemmed	Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>
title_sort	mixed infections and <italic toggle="yes">in vivo</italic> evolution in the human fungal pathogen <named-content content-type="genus-species">cryptococcus neoformans</named-content>
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/c6a2378839c746d399e035702774b558
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Mixed Infections and <italic toggle="yes">In Vivo</italic> Evolution in the Human Fungal Pathogen <named-content content-type="genus-species">Cryptococcus neoformans</named-content>

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