title: Binding of the wheat germ lectin to Cryptococcus neoformans chitooligomers affects multiple mechanisms required for fungal pathogenesis.
abstract: The principal capsular component of Cryptococcus neoformans, glucuronoxylomannan (GXM), interacts with surface glycans, including chitin-like oligomers. Although the role of GXM in cryptococcal infection has been well explored, there is no information on how chitooligomers affect fungal pathogenesis. In this study, surface chitooligomers of C. neoformans were blocked through the use of the wheat germ lectin (WGA) and the effects on animal pathogenesis, interaction with host cells, fungal growth and capsule formation were analyzed. Treatment of C. neoformans cells with WGA followed by infection of mice delayed mortality relative to animals infected with untreated fungal cells. This observation was associated with reduced brain colonization by lectin-treated cryptococci. Blocking chitooligomers also rendered yeast cells less efficient in their ability to associate with phagocytes. WGA did not affect fungal viability, but inhibited GXM release to the extracellular space and capsule formation. In WGA-treated yeast cells, genes that are involved in capsule formation and GXM traffic had their transcription levels decreased in comparison with untreated cells. Our results suggest that cellular pathways required for capsule formation and pathogenic mechanisms are affected by blocking chitin-derived structures at the cell surface of C. neoformans. Targeting chitooligomers with specific ligands may reveal new therapeutic alternatives to control cryptococcosis.
authors.affiliation: Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Fonseca
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Guimarães
authors.forename: Lívia
authors.initials: L
authors.lastname: Kmetzsch
authors.forename: Fabianno F
authors.initials: FF
authors.lastname: Dutra
authors.forename: Fernanda D
authors.initials: FD
authors.lastname: Silva
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Taborda
authors.forename: Glauber de S
authors.initials: Gde S
authors.lastname: Araujo
authors.forename: Susana
authors.initials: S
authors.lastname: Frases
authors.forename: Charley C
authors.initials: CC
authors.lastname: Staats
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Bozza
authors.forename: Augusto
authors.initials: A
authors.lastname: Schrank
authors.forename: Marilene H
authors.initials: MH
authors.lastname: Vainstein
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D001921:Brain / Q000382:microbiology; D002686:Chitin / Q000378:metabolism; D003453:Cryptococcosis / Q000188:drug therapy / Q000473:pathology; D003455:Cryptococcus neoformans / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D062607:Fungal Capsules / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects*; D011134:Polysaccharides / Q000378:metabolism*; D014909:Wheat Germ Agglutinins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011134:Polysaccharides; D014909:Wheat Germ Agglutinins; D002686:Chitin; C027478:glucuronoxylomannan
keywords: Capsule; Chitin oligosaccharides; Cryptococcus neoformans; Lectin binding; Virulence