The AGC Kinase YpkA Regulates Sphingolipids Biosynthesis and Physically Interacts With SakA MAP Kinase in Aspergillus fumigatus

Autor(es)

Tadini Marilhano Fabri, Joao Henrique ^[1] ; Godoy, Naiane Lima ^[1] ; Rocha, Marina Campos ^[1] ; Munshi, Mansa ^[2] ; Cocio, Tiago Alexandre ^{[1, 3]} ; von Zeska Kress, Marcia Regina ^[4] ; Fill, Taicia Pacheco ^[5] ; da Cunha, Anderson Ferreira ^[1] ; Del Poeta, Maurizio ^{[6, 7, 8]} ; Malavazi, Iran ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Genet & Evolucao, Ctr Ciencias Biol & Saude, Sao Carlos, SP - Brazil

^[2] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 - USA

^[3] Univ Sao Paulo, Hosp Clin Ribeirao Preto, Fac Med Ribeirao Preto, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto - Brazil

^[5] Univ Estadual Campinas, Inst Quim, Campinas, SP - Brazil

^[6] SUNY Stony Brook, Sch Med, Div Infect Dis, Stony Brook, NY 11794 - USA

^[7] SUNY Stony Brook, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 - USA

^[8] Vet Adm Med Ctr, Northport, NY - USA

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 9, JAN 14 2019.
• Citações Web of Science: 1

Resumo

Sphingolipids (SL) are complex lipids and components of the plasma membrane which are involved in numerous cellular processes, as well as important for virulence of different fungal pathogens. In yeast, SL biosynthesis is regulated by the ``AGC kinases{''} Ypk1 and Ypk2, which also seem to connect the SL biosynthesis with the cell wall integrity (CWI) and the High Osmolarity Glycerol (HOG) pathways. Here, we investigate the role of ypkA(YPK1) in SL biosynthesis and its relationship with the CWI and the HOG pathways in the opportunistic human pathogen Aspergillus fumigatus. We found that ypkA is important for fungal viability, since the 1 ypkA strain presented a drastically sick phenotype and complete absence of conidiation. We observed that under repressive condition, the conditional mutant niiA::ypkA exhibited vegetative growth defects, impaired germination and thermosensitivity. In addition, the ypkA loss of function caused a decrease in glycosphingolipid (GSL) levels, especially the metabolic intermediates belonging to the neutral GSL branch including dihydroceramide (DHC), ceramide (Cer), and glucosylceramide (GlcCer), but interestingly a small increase in ergosterol content. Genetic analyzes showed that ypkA genetically interacts with the MAP kinases of CWI and HOG pathways, mpkA and sakA, respectively, while only SakA physically interacts with YpkA. Our results suggest that YpkA is important for fungal survival through the regulation of GSL biosynthesis and cross talks with A. fumigatus MAP kinase pathways. (AU)

• Processo FAPESP: 09/53546-5 - Caracterização molecular da via de sinalização celular mediada pela proteína Quinase C no fungo patogênico humano Aspergillus fumigatus
• Beneficiário: Iran Malavazi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/17541-0 - Estudo da relação da via da integridade da parede celular e de genes de resposta ao estresse térmico no fungo patogênico humano Aspergillus fumigatus
• Beneficiário: Iran Malavazi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/19694-3 - Identificação do papel das proteínas de choque térmico HsfA e Hsp90 e do regulador SmiA na atividade da via da integridade da parede celular no fungo patogênico oportunista humano Aspergillus fumigatus
• Beneficiário: Iran Malavazi
• Modalidade de apoio: Auxílio à Pesquisa - Regular