Phenotypic Variability Correlates with Clinical Outcome in Cryptococcus Isolates Obtained from Botswanan HIV/AIDS Patients

Author:

Fernandes Kenya E.1,Brockway Adam1,Haverkamp Miriam2,Cuomo Christina A.3ORCID,van Ogtrop Floris1,Perfect John R.4,Carter Dee A.1ORCID

Affiliation:

1. School of Life and Environmental Sciences and the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, New South Wales, Australia

2. Faculty of Medicine, University of Botswana, Gaborone, Botswana

3. Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA

4. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

Abstract

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.

Funder

Australian Postgraduate Award

Public Health Service Grant

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

Reference55 articles.

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4. Global Action Fund for Fungal Infections (GAFFI). 2017. Cryptococcal meningitis fact sheet. Global Action Fund for Fungal Infections (GAFFI) Geneva Switzerland. Accessed 21 May 2018. https://www.gaffi.org/wp-content/uploads/Cryptococcal-meningitis-Fact-Sheet.pdf.

5. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

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