title: Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection.
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 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US.
authors.forename: Radames J B
authors.initials: RJ
authors.lastname: Cordero
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, Brazil.
authors.forename: Susie Coutinho
authors.initials: SC
authors.lastname: Liedke
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro &Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Rio de Janeiro, Brazil.
authors.forename: Glauber R
authors.initials: GR
authors.lastname: de S Araújo
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine; New York Institute of Technology; Old Westbury, NY, US.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
authors.affiliation: Laboratório de Glicobiologia de Eucariotos, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro &Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Rio de Janeiro, Brazil.
authors.forename: Susana
authors.initials: S
authors.lastname: Frases
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, Brazil.
authors.forename: Jose Mauro
authors.initials: JM
authors.lastname: Peralta
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US.
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.affiliation: Laboratório de Biologia Celular de Leveduras Patogênicas, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ. Brazil.|Fundação Oswaldo Cruz - Fiocruz, Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil.
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, US.|Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, US.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.affiliation: Departamento de Microbiologia e Parasitologia, Instituto Biomédico, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Guimaraes
mesh_terms: D000818:Animals; D060085:Coinfection / Q000382:microbiology*; D003453:Cryptococcosis / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000502:physiology*; D005260:Female; D062610:Fungal Polysaccharides / Q000502:physiology*; D006658:Histoplasma / Q000472:pathogenicity*; D006660:Histoplasmosis / Q000382:microbiology*; D017737:Macrophages, Peritoneal / Q000382:microbiology / Q000502:physiology; D008810:Mice, Inbred C57BL; D056265:Microbial Interactions; D014774:Virulence
chemical_list: D062610:Fungal Polysaccharides