title: Functional analysis of Paracoccidioides brasiliensis 14-3-3 adhesin expressed in Saccharomyces cerevisiae.
abstract: BACKGROUND
  14-3-3 proteins comprise a family of eukaryotic multifunctional proteins involved in several cellular processes. The Pb14-3-3 of Paracoccidioides brasiliensis seems to play an important role in the Paracoccidioides-host interaction. Paracoccidioides brasiliensis is an etiological agent of paracoccidioidomycosis, which is a systemic mycosis that is endemic in Latin America. In the initial steps of the infection, Paracoccidioides spp. synthetizes adhesins that allow it to adhere and invade host cells. Therefore, the aim of this work was to perform a functional analysis of Pb14-3-3 using Saccharomyces cerevisiae as a model.
  
  
  RESULTS
  The functional analysis of Pb14-3-3 was performed in S. cerevisiae, and it was found that Pb14-3-3 partially complemented S. cerevisiae proteins Bmh1p and Bmh2p, which are recognized as two yeast 14-3-3 homologues. When we evaluated the adhesion profile of S. cerevisiae transformants, Pb14-3-3 acted as an adhesin in S. cerevisiae; however, Bmh1p did not show this function. The influence of Pb14-3-3 in S. cerevisiae ergosterol pathway was also evaluated and our results showed that Pb14-3-3 up-regulates genes involved in ergosterol biosynthesis.
  
  
  CONCLUSIONS
  Our data showed that Pb14-3-3 was able to partially complement Bmh1p and Bmh2p proteins in S. cerevisiae; however, we suggest that Pb14-3-3 has a differential role as an adhesin. In addition, Pb-14-3-3 may be involved in Paracoccidioides spp. ergosterol biosynthesis which makes it an interest as a therapeutic target.
authors.affiliation: Laboratório de Micologia Clínica - Núcleo de Proteômica - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. patricia.assato@gmail.com.
authors.forename: Patricia Akemi
authors.initials: PA
authors.lastname: Assato
authors.affiliation: Laboratório de Micologia Clínica - Núcleo de Proteômica - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. julhiany.silva@gmail.com.
authors.forename: Julhiany de Fátima
authors.initials: Jde F
authors.lastname: da Silva
authors.affiliation: Laboratório de Micologia Clínica - Núcleo de Proteômica - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. haroldocdoliveira@gmail.com.
authors.forename: Haroldo Cesar
authors.initials: HC
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Micologia Clínica - Núcleo de Proteômica - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. marcos_caroline@yahoo.com.br.
authors.forename: Caroline Maria
authors.initials: CM
authors.lastname: Marcos
authors.affiliation: Laboratório de Biologia Molecular - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. danuzarossi@uol.com.br.
authors.forename: Danuza
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Laboratório de Biologia Molecular - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. valentsr@fcfar.unesp.br.
authors.forename: Sandro Roberto
authors.initials: SR
authors.lastname: Valentini
authors.affiliation: Laboratório de Micologia Clínica - Núcleo de Proteômica - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. giannini@fcfar.unesp.br.
authors.forename: Maria José Soares
authors.initials: MJ
authors.lastname: Mendes-Giannini
authors.affiliation: Laboratório de Biologia Molecular - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. zanellicf@fcfar.unesp.br.
authors.forename: Cleslei Fernando
authors.initials: CF
authors.lastname: Zanelli
authors.affiliation: Laboratório de Micologia Clínica - Núcleo de Proteômica - Faculdade de Ciências Farmacêuticas- Unesp - Campus Araraquara, Rodovia Araraquara - Jaú Km 1, 14801-902, Araraquara, SP, Brazil. ana.marisa@uol.com.br.
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Fusco-Almeida
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D004875:Ergosterol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005816:Genetic Complementation Test; D010228:Paracoccidioides / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; C075852:BMH1 protein, S cerevisiae; C097164:BMH2 protein, S cerevisiae; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D004875:Ergosterol