TY - JOUR
T1 - Binding of the wheat germ lectin to Cryptococcus neoformans chitooligomers affects multiple mechanisms required for fungal pathogenesis
AU - Fonseca, Fernanda L.
AU - Guimarães, Allan J.
AU - Kmetzsch, Lívia
AU - Dutra, Fabianno F.
AU - Silva, Fernanda D.
AU - Taborda, Carlos P.
AU - Araujo, Glauber de S.
AU - Frases, Susana
AU - Staats, Charley C.
AU - Bozza, Marcelo T.
AU - Schrank, Augusto
AU - Vainstein, Marilene H.
AU - Nimrichter, Leonardo
AU - Casadevall, Arturo
AU - Rodrigues, Marcio L.
N1 - Funding Information:
We thank Radames Cordero, Julian Muñoz, Antonio Nakouzi and Lorena Derengowski for suggestions and help with animal experimentation. M.L.R., A.S., C.C.S., M.H.V., F.L.F., C.P.T., A.J.G., M.T.B., C.P.T., and L.N. are supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP, Brazil) and Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil). A.C. is supported by NIH Grants AI033142, AI033774, AI052733, and HL059842 and the Center for AIDS Research at Einstein. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no reported conflicts of interest.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Capsule
KW - Chitin oligosaccharides
KW - Cryptococcus neoformans
KW - Lectin binding
KW - Virulence
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UR - http://www.scopus.com/inward/citedby.url?scp=84887615780&partnerID=8YFLogxK
U2 - 10.1016/j.fgb.2013.04.005
DO - 10.1016/j.fgb.2013.04.005
M3 - Article
C2 - 23608320
AN - SCOPUS:84887615780
SN - 1087-1845
VL - 60
SP - 64
EP - 73
JO - Fungal Genetics and Biology
JF - Fungal Genetics and Biology
ER -