Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients

ABSTRACT Pathogenic species of Cryptococcus cause hundreds of thousands of deaths annually. Considerable phenotypic variation is exhibited during infection, including increased capsule size, capsule shedding, giant cells (≥15 μm), and micro cells (≤1 μm). We examined 70 clinical isolates of Cryptoco...

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Autores principales:	Kenya E. Fernandes, Adam Brockway, Miriam Haverkamp, Christina A. Cuomo, Floris van Ogtrop, John R. Perfect, Dee A. Carter
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Cryptococcus capsule cell size meningitis pleomorphism yeasts Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e1e48f1ce27247bdb21547fce1bf3298
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spelling	oai:doaj.org-article:e1e48f1ce27247bdb21547fce1bf32982021-11-15T15:58:21ZPhenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients10.1128/mBio.02016-182150-7511https://doaj.org/article/e1e48f1ce27247bdb21547fce1bf32982018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02016-18https://doaj.org/toc/2150-7511ABSTRACT Pathogenic species of Cryptococcus cause hundreds of thousands of deaths annually. Considerable phenotypic variation is exhibited during infection, including increased capsule size, capsule shedding, giant cells (≥15 μm), and micro cells (≤1 μm). We examined 70 clinical isolates of Cryptococcus neoformans and Cryptococcus tetragattii from HIV/AIDS patients in Botswana to determine whether the capacity to produce morphological variants was associated with clinical parameters. Isolates were cultured under conditions designed to simulate in vivo stresses. Substantial variation was seen across morphological and clinical data. Giant cells were more common in C. tetragattii, while micro cells and shed capsule occurred in C. neoformans only. Phenotypic variables fell into two groups associated with differing symptoms. The production of “large” phenotypes (greater cell and capsule size and giant cells) was associated with higher CD4 count and was negatively correlated with intracranial pressure indicators, suggesting that these are induced in early stage infection. “Small” phenotypes (micro cells and shed capsule) were associated with lower CD4 counts, negatively correlated with meningeal inflammation indicators, and positively correlated with intracranial pressure indicators, suggesting that they are produced later during infection and may contribute to immune suppression and promote proliferation and dissemination. These trends persisted at the species level, indicating that they were not driven by association with particular Cryptococcus species. Isolates possessing giant cells, micro cells, and shed capsule were rare, but strikingly, they were associated with patient death (P = 0.0165). Our data indicate that pleomorphism is an important driver in Cryptococcus infection. IMPORTANCE Cryptococcosis results in hundreds of thousands of deaths annually, predominantly in sub-Saharan Africa. Cryptococcus is an encapsulated yeast, and during infection, cells have the capacity for substantial morphological changes, including capsule enlargement and shedding and variations in cell shape and size. In this study, we examined 70 Cryptococcus isolates causing meningitis in HIV/AIDS patients in Botswana in order to look for associations between phenotypic variation and clinical symptoms. Four variant phenotypes were seen across strains: giant cells of ≥15 µm, micro cells of ≤1 µm, shed extracellular capsule, and irregularly shaped cells. We found that “large” and “small” phenotypes were associated with differing disease symptoms, indicating that their production may be important during the disease process. Overall, our study indicates that Cryptococcus strains that can switch on cell types under different situations may be more able to sustain infection and resist the host response.Kenya E. FernandesAdam BrockwayMiriam HaverkampChristina A. CuomoFloris van OgtropJohn R. PerfectDee A. CarterAmerican Society for MicrobiologyarticleCryptococcuscapsulecell sizemeningitispleomorphismyeastsMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cryptococcus capsule cell size meningitis pleomorphism yeasts Microbiology QR1-502
spellingShingle	Cryptococcus capsule cell size meningitis pleomorphism yeasts Microbiology QR1-502 Kenya E. Fernandes Adam Brockway Miriam Haverkamp Christina A. Cuomo Floris van Ogtrop John R. Perfect Dee A. Carter Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients
description	ABSTRACT Pathogenic species of Cryptococcus cause hundreds of thousands of deaths annually. Considerable phenotypic variation is exhibited during infection, including increased capsule size, capsule shedding, giant cells (≥15 μm), and micro cells (≤1 μm). We examined 70 clinical isolates of Cryptococcus neoformans and Cryptococcus tetragattii from HIV/AIDS patients in Botswana to determine whether the capacity to produce morphological variants was associated with clinical parameters. Isolates were cultured under conditions designed to simulate in vivo stresses. Substantial variation was seen across morphological and clinical data. Giant cells were more common in C. tetragattii, while micro cells and shed capsule occurred in C. neoformans only. Phenotypic variables fell into two groups associated with differing symptoms. The production of “large” phenotypes (greater cell and capsule size and giant cells) was associated with higher CD4 count and was negatively correlated with intracranial pressure indicators, suggesting that these are induced in early stage infection. “Small” phenotypes (micro cells and shed capsule) were associated with lower CD4 counts, negatively correlated with meningeal inflammation indicators, and positively correlated with intracranial pressure indicators, suggesting that they are produced later during infection and may contribute to immune suppression and promote proliferation and dissemination. These trends persisted at the species level, indicating that they were not driven by association with particular Cryptococcus species. Isolates possessing giant cells, micro cells, and shed capsule were rare, but strikingly, they were associated with patient death (P = 0.0165). Our data indicate that pleomorphism is an important driver in Cryptococcus infection. IMPORTANCE Cryptococcosis results in hundreds of thousands of deaths annually, predominantly in sub-Saharan Africa. Cryptococcus is an encapsulated yeast, and during infection, cells have the capacity for substantial morphological changes, including capsule enlargement and shedding and variations in cell shape and size. In this study, we examined 70 Cryptococcus isolates causing meningitis in HIV/AIDS patients in Botswana in order to look for associations between phenotypic variation and clinical symptoms. Four variant phenotypes were seen across strains: giant cells of ≥15 µm, micro cells of ≤1 µm, shed extracellular capsule, and irregularly shaped cells. We found that “large” and “small” phenotypes were associated with differing disease symptoms, indicating that their production may be important during the disease process. Overall, our study indicates that Cryptococcus strains that can switch on cell types under different situations may be more able to sustain infection and resist the host response.
format	article
author	Kenya E. Fernandes Adam Brockway Miriam Haverkamp Christina A. Cuomo Floris van Ogtrop John R. Perfect Dee A. Carter
author_facet	Kenya E. Fernandes Adam Brockway Miriam Haverkamp Christina A. Cuomo Floris van Ogtrop John R. Perfect Dee A. Carter
author_sort	Kenya E. Fernandes
title	Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients
title_short	Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients
title_full	Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients
title_fullStr	Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients
title_full_unstemmed	Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients
title_sort	phenotypic variability correlates with clinical outcome in <italic toggle="yes">cryptococcus</italic> isolates obtained from botswanan hiv/aids patients
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/e1e48f1ce27247bdb21547fce1bf3298
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Phenotypic Variability Correlates with Clinical Outcome in <italic toggle="yes">Cryptococcus</italic> Isolates Obtained from Botswanan HIV/AIDS Patients

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