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

Radames J B Cordero, Susie Coutinho Liedke, Glauber R De S Araújo, Luis R. Martinez, Leonardo Nimrichter, Susana Frases, Jose Mauro Peralta, Arturo Casadevall, Marcio L. Rodrigues, Joshua D. Nosanchuk, Allan J. Guimaraes

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article number21765
JournalScientific Reports
Volume6
DOIs
StatePublished - Feb 24 2016

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Histoplasma
Cryptococcus neoformans
Coinfection
Polysaccharides
Virulence
Infection
Microbial Interactions
Mycoses
Virulence Factors
Phagocytosis
Fungi
Macrophages
Lung
Temperature
Mortality

ASJC Scopus subject areas

  • General

Cite this

Cordero, R. J. B., Liedke, S. C., Araújo, G. R. D. S., Martinez, L. R., Nimrichter, L., Frases, S., ... Guimaraes, A. J. (2016). Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection. Scientific Reports, 6, [21765]. https://doi.org/10.1038/srep21765

Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection. / Cordero, Radames J B; Liedke, Susie Coutinho; Araújo, Glauber R De S; Martinez, Luis R.; Nimrichter, Leonardo; Frases, Susana; Peralta, Jose Mauro; Casadevall, Arturo; Rodrigues, Marcio L.; Nosanchuk, Joshua D.; Guimaraes, Allan J.

In: Scientific Reports, Vol. 6, 21765, 24.02.2016.

Research output: Contribution to journalArticle

Cordero, RJB, Liedke, SC, Araújo, GRDS, Martinez, LR, Nimrichter, L, Frases, S, Peralta, JM, Casadevall, A, Rodrigues, ML, Nosanchuk, JD & Guimaraes, AJ 2016, 'Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection', Scientific Reports, vol. 6, 21765. https://doi.org/10.1038/srep21765
Cordero, Radames J B ; Liedke, Susie Coutinho ; Araújo, Glauber R De S ; Martinez, Luis R. ; Nimrichter, Leonardo ; Frases, Susana ; Peralta, Jose Mauro ; Casadevall, Arturo ; Rodrigues, Marcio L. ; Nosanchuk, Joshua D. ; Guimaraes, Allan J. / Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection. In: Scientific Reports. 2016 ; Vol. 6.
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