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

Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brazil.
Department of Biomedical Sciences. College of Osteopathic Medicine. New York Institute of Technology. Old Westbury, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Glicobiologia de Eucariotos. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Ultraestrutura Celular Hertha Meyer. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brazil.
Department of Molecular Microbiology and Immunology. Johns Hopkins Bloomberg School of Public Health. Baltimore, USA.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Laboratório de Biologia Celular de Leveduras Patogênicas. Rio de Janeiro, RJ, Brazil / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.
Department of Microbiology and Immunology. Albert Einstein College of Medicine. Yeshiva University. Bronx, USA / Department of Medicine (Division of Infectious Diseases). Albert Einstein College of Medicine. Yeshiva University. Bronx, USA.
Universidade Federal Fluminense. Instituto Biomédico. Departamento de Microbiologia e Parasitologia. Rio de Janeiro, RJ, Brazil.

Resumo em Inglês

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 involving the transfer of virulence traits that translates into enhanced lethality during mixed fungal infections and highlights the importance of studying heterogeneous microbial populations in the setting of infection.

Palavras-chave em inglês

Histoplasma capsulatum
Cryptococcus neoformans
Invasive fungal-infections
Cutaneous cryptococcosis
Mycoses
Microbial interactions
Ppolysaccharide
Fungal polysaccharides

Editor

Nature Publishing Group

Referência

CORDERO, Radames J. B. et al. Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection. Scientific Reports, v. 6, p. 1-16, Feb. 2016.

DOI

10.1038/SREP21765

ISSN

2045-2322

Use este identificador para citar ou linkar para este item: https://www.arca.fiocruz.br/handle/icict/59628

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