Immunoproteomic analysis reveals a convergent humoral response signature in the Sporothrix schenckii complex

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dc.contributor.authorRodrigues, Anderson Messias [UNIFESP]
dc.contributor.authorKubitschek-Barreira, Paula H.
dc.contributor.authorFernandes, Geisa Ferreira [UNIFESP]
dc.contributor.authorAlmeida, Sandro Rogerio de
dc.contributor.authorLopes-Bezerra, Leila M.
dc.contributor.authorCamargo, Zoilo Pires de [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade do Estado do Rio de Janeiro (UERJ)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T14:40:03Z
dc.date.available2016-01-24T14:40:03Z
dc.date.issued2015-02-06
dc.description.abstractSporotrichosis is a polymorphic disease that affects both humans and animals worldwide. the fungus gains entry into a warm-blooded host through minor trauma to the skin, typically by contaminated vegetation or by scratches and bites from a diseased cat. Cellular and humoral responses triggered upon pathogen introduction play important roles in the development and severity of the disease. We investigated molecules expressed during the host parasite interplay that elicit the humoral response in human sporotrichosis. for antigenic profiling, Sporothrix yeast cell extracts were separated by two-dimensional (2D) gel electrophoresis and probed with pooled sera from individuals with fixed cutaneous and lymphocutaneous sporotrichosis. Thirty-five IgG-seroreactive spots were identified as eight specific proteins by MALDI ToF/MS. Remarkable cross-reactivity among Sporothrix brasiliensis, Sporothrix schenckii, and Sporothrix globosa was noted and antibodies strongly reacted with the 70-kDa protein (gp70), irrespective of clinical manifestation. Gp70 was successfully identified in multiple spots as 3-carboxymuconate cyclase. in addition, 2D-DIGE characterization suggested that the major antigen of sporotrichosis undergoes post-translational modifications involving glycosylation and amino acid substitution, resulting in at least six isoforms and glycoforms that were present in the pathogenic species but absent in the ancestral non-virulent Sporothrix mexicana. Although a primary environmental function related to the benzoate degradation pathway of aromatic polymers has been attributed to orthologs of this molecule, our findings support the hypothesis that gp70 is important for pathogenesis and invasion in human sporotrichosis. We propose a diverse panel of new putative candidate molecules for diagnostic tests and vaccine development.Biological significanceOutbreaks due to Sporothrix spp. have emerged over time, affecting thousands of patients worldwide. A sophisticated host pathogen interplay drives the manifestation and severity of infection, involving immune responses elicited upon traumatic exposure of the skin barrier to the pathogen followed by immune evasion. Using an immunoproteomic approach we characterized proteins of potential significance in pathogenesis and invasion that trigger the humoral response during human sporotrichosis. We found gp70 to be a cross-immunogenic protein shared among pathogenic Sporothrix spp. but absent in the ancestral environmental S. mexicana, supporting the hypothesis that gp70 plays key roles in pathogenicity. for the first time, we demonstrate with 2D-DIGE that post-translational modifications putatively involve glycosylation and amino acid substitution, resulting in at least six isoforms and glycoforms, all of them IgG-reactive. These findings of a convergent humoral response highlight gp70 as an important target serological diagnosis and for vaccine development among phylogenetically related agents of sporotrichosis. (C) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Div Cell Biol, UNIFESP, BR-04023062 São Paulo, SP, Brazil
dc.description.affiliationUniv Estado Rio de Janeiro, Roberto Alcantara Gomes Inst Biol, Dept Cellular Biol, Rio de Janeiro, Brazil
dc.description.affiliationUniv São Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, São Paulo, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Div Cell Biol, UNIFESP, BR-04023062 São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIDFAPESP: 2009/54024-2
dc.description.sponsorshipIDCNPq: 472600/2011-7
dc.format.extent8-22
dc.identifierhttp://dx.doi.org/10.1016/j.jprot.2014.11.013
dc.identifier.citationJournal of Proteomics. Amsterdam: Elsevier B.V., v. 115, p. 8-22, 2015.
dc.identifier.doi10.1016/j.jprot.2014.11.013
dc.identifier.issn1874-3919
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/38754
dc.identifier.wosWOS:000350184200002
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of Proteomics
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectSporotrichosisen
dc.subjectgp70en
dc.subject3-Carboxymuconate cyclaseen
dc.subjectGlycoformsen
dc.subjectIsoformen
dc.subject2D-DIGEen
dc.titleImmunoproteomic analysis reveals a convergent humoral response signature in the Sporothrix schenckii complexen
dc.typeinfo:eu-repo/semantics/article
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