Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection

Scientific Reports
Radames J B CorderoAllan J Guimaraes

Abstract

Cryptococcus neoformans (Cn) and Histoplasma capsulatum (Hc) co-exist in the environment and occasionally co-infect individuals, which can lead to severe disease/lethal outcomes. We investigated specific interactions between Cn-Hc to determine the impact of synchronous infection in virulence and disease. Co-infected mice had significantly higher mortality than infection with either species or acapsular Cn-Hc. Coating of Hc with cryptococcal glycans (Cn-gly) resulted in higher pulmonary fungal burden in co-infected animals relative to control. Co-cultivation or addition of Cn-gly resulted in enhanced pellicle formation with a hybrid polysaccharide matrix with higher reactivity to GXM mAbs. Transfer and incorporation of Cn polysaccharide onto Hc surface was time and temperature dependent. Cn-gly transfer altered the zeta potential of Hc and was associated with increased resistance to phagocytosis and killing by macrophages. Mice infected with Hc and subsequently injected with purified Cn-gly died significantly more rapidly than Hc alone infected, establishing the precedent that virulence factors from one fungus can enhance the virulence of unrelated species. These findings suggest a new mechanism of microbial interaction involvin...Continue Reading

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Citations

Oct 24, 2018·Journal of Fungi·Junya L SingulaniMaria José S Mendes-Giannini
Apr 12, 2018·Memórias do Instituto Oswaldo Cruz·Carolina FiracativeUNKNOWN Latin American Cryptococcal Study Group
Aug 6, 2020·Frontiers in Microbiology·Larissa Naiara Carvalho GonçalvesAna Marisa Fusco-Almeida
Jan 30, 2021·Applied Microbiology and Biotechnology·Ivica DimkićMilica Ljaljević Grbić
Oct 31, 2020·Journal of Fungi·Claudia Rodriguez-de la NovalAllan J Guimarães
Feb 16, 2021·Frontiers in Cellular and Infection Microbiology·Diego de Souza GonçalvesAllan J Guimarães
Aug 17, 2021·European Journal of Immunology·Gustavo J C Freitas, Daniel A Santos

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Methods Mentioned

BETA
fluorescence microscopy
flow cytometry
ELISA
FACS
environmental stress

Software Mentioned

GraphPad
GraphPad Prism

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