Immunoproteomics reveals pathogen?s antigens involved in Homo sapiens- Histoplasma capsulatum interaction and specific linear B-cell epitopes in histoplasmosis
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2020
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Resumo
Histoplasmosis is one of the most frequent systemic mycosis in HIV patients. In these
patients, histoplasmosis has high rates of morbidity/mortality if diagnosis and treatment
are delayed. Despite its relevance, there is a paucity of information concerning the
interaction between Histoplasma capsulatum and the human host, especially regarding
the B-cell response, which has a direct impact on the diagnosis. Culture-based “gold standard” methods have limitations, making immunodiagnostic tests an attractive option
for clinical decisions. Despite the continuous development of those tests, improving
serological parameters is necessary to make these methods efficient tools for definitive
diagnosis of histoplasmosis. This includes the determination of more specific and
immunogenic antigens to improve specificity and sensitivity of assays. In this study, we
performed a co-immunoprecipitation assay between a protein extract from the yeast form
of H. capsulatum and pooled sera from patients with proven histoplasmosis, followed by
shotgun mass spectrometry identification of antigenic targets. Sera from patients with
other pulmonary infections or from healthy individuals living in endemic areas of
histoplasmosis were also assayed to determine potentially cross-reactive proteins. The
primary structures of H. capsulatum immunoprecipitated proteins were evaluated using
the DNAStar Protean 7.0 software. In parallel, the online epitope prediction server,
BCPREDS, was used to complement the B-epitope prediction analysis. Our approach
detected 132 reactive proteins to antibodies present in histoplasmosis patients’ sera.
Among these antigens, 127 were recognized also by antibodies in heterologous patients’
and/or normal healthy donors’ sera. Therefore, the only three antigens specifically
recognized by antibodies of histoplasmosis patients were mapped as potential antigenic targets: the M antigen, previously demonstrated in the diagnosis of
histoplasmosis, and the catalase P and YPS-3 proteins, characterized as virulence
factors of H. capsulatum, with antigenic properties still unclear. The other two proteins
were fragments of the YPS-3 and M antigen. Overlapping results obtained from the two
aforementioned bioinformatic tools, 16 regions from these three proteins are proposed as
putative B-cell epitopes exclusive to H. capsulatum. These data reveal a new role for these
proteins on H. capsulatum interactions with the immune system and indicate their
possible use in new methods for the diagnosis of histoplasmosis.
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Histoplasma capsulatum, Homo sapiens, Immunoproteome, Mass spectrometry, Epitopes, M antigen, YPS-3, Catalase P
Citação
ALMEIDA, Marcos Abreu et al. Immunoproteomics reveals pathogen's antigens involved in Homo sapiens-Histoplasma capsulatum interaction and specific linear B-cell epitopes in histoplasmosis. Frontiers in Cellular and Infection Microbiology, Lausanne, v. 10, e591121, 2020. DOI: 10.3389/fcimb.2020.591121. Disponível em: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.591121/full. Acesso em: 22 nov. 2024.