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Phenotypic Plasticity in the Productions of Virulence Factors Within and Among Serotypes in the Cryptococcus neoformans Species Complex

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Abstract

The Cryptococcus neoformans species complex (CNSC) is a common opportunistic human fungal pathogen and the most frequent cause of fungal meningitis. There are three major serotypes in CNSC: A, D, and their hybrids AD, and they have different geographic distributions and medical significance. Melanin pigment and a polysaccharide capsule are the two major virulence factors in CNSC. However, the relationships between serotype and virulence factor production and how environmental factors might impact their relationships are not known. This study investigated the expressions of melanin and capsular polysaccharide in a genetically diverse group of CNSC strains and how their phenotypic expressions were influenced by oxidative and nitrosative stress levels. We found significant differences in melanin and capsular polysaccharide productions among serotypes and across stress conditions. Under oxidative stress, the laboratory hybrids exhibited the highest phenotypic plasticity for melanin production while serotype A showed the highest for capsular polysaccharide production. In contrast, serotype D exhibited the highest phenotypic plasticity for capsular polysaccharide production and clinical serotype AD the highest phenotypic plasticity for melanin production under nitrosative stress. These results demonstrated that different serotypes have different environmental condition-specific mechanisms to modulate the expression of virulence factors.

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All data described in the study are presented in the manuscript and as supplementary files.

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Acknowledgements

We thank Dr. Max Cogliati, Dr. Volker Rickerts, Dr. Tracey Moore, and Himeshi Samarasinghe for strains. This study was supported by grants from the Natural Sciences and Engineering Research Council (NSERC) of Canada and by the Institute of Infectious Diseases Research at McMaster University.

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Correspondence to Jianping Xu.

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Iyengar, Y., Xu, J. Phenotypic Plasticity in the Productions of Virulence Factors Within and Among Serotypes in the Cryptococcus neoformans Species Complex. Mycopathologia 187, 65–83 (2022). https://doi.org/10.1007/s11046-021-00597-3

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