Paracoccidioides lutzii e outros fungos de importância médica: desenvolvimento de vacina terapêutica e tratamento alternativo com compostos sintéticos no controle das micoses sistêmicas.

Rossi, Diego Conrado Pereira

doi:10.11606/T.42.2018.tde-14072017-142047

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DOI

https://doi.org/10.11606/T.42.2018.tde-14072017-142047

Document

Doctoral Thesis

Author

Rossi, Diego Conrado Pereira (Catálogo USP)

Full name

Diego Conrado Pereira Rossi

Institute/School/College

Instituto de Ciências Biomédicas

Knowledge Area

Microbiology

Date of Defense

2017-03-24

Published

São Paulo, 2017

Supervisor

Taborda, Carlos Pelleschi (Catálogo USP)

Committee

Taborda, Carlos Pelleschi (President)
Almeida, Sandro Rogerio de
Bezerra, Leila Maria Lopes
Correa, Benedito
Ferreira, Karen Spadari

Title in Portuguese

Paracoccidioides lutzii e outros fungos de importância médica: desenvolvimento de vacina terapêutica e tratamento alternativo com compostos sintéticos no controle das micoses sistêmicas.

Keywords in Portuguese

Candidíase
Criptococose
Desenvolvimento de vacinas
Micoses de interesse médico
Paracoccidioidomicose

Abstract in Portuguese

A maioria dos tratamentos antifúngicos são longos e não eficazes, portanto, há uma necessidade de pesquisa de novas alternativas. A fim de prospectar novos epitopos para uma vacina para Paracoccidioides lutzii e Cryptococcus spp.. Foi desenvolvido um sistema com o objetivo de purificar epitopos de macrófagos no contexto de MHCII. Além disso, houve pesquisa de epítopos na parede celular e sobrenadante de Paracoccidioides spp. A atividade antifúngica da miltefosina foi avaliada contra Paracoccicioides spp.. A miltefosina demonstrou atividade inibitória similar à anfotericina B. A atividade fungicida ocorreu em baixas concentrações, se observou alterações ultraestruturais e formação de melanina. A atividade do C7a in vitro e in vivo contra Candida spp. foi analisada. Os resultados mostraram atividade fungicida em valores baixos. Além disso, foi visto inibição da formação de hifas / pseudohifas e alterações morfológicas. Os ensaios in vivo demonstraram uma diminuição significativa na infecção em um modelo de candidíase vaginal e sistêmica.

Title in English

Paracoccidioides lutzii and other fungi of medical importance: development of therapeutic vaccine and alternative treatment with synthetic compounds in the control of systemic mycoses.

Keywords in English

Candidiasis
Cryptococcosis
Development of vaccines
Mycoses of medical interest
Paracoccidioidomycosis

Abstract in English

Most of antifungal treatments are not completely effective or long, thus there is a need to search new alternatives. In order to prospect new epitopes for a vaccine to Paracoccidioides lutzii and Cryptococcus spp.. A system was developed with the purpose of purify epitopes from macrophages in the context of MHCII. Also, a search for epitopes in the cell wall and supernatant of Paracoccidioides spp. was done. The antifungal activity of miltefosina was evaluated against Paracoccicioides spp.. Miltefosine demonstrated inhibitory activity similar to amphotericin B. Fungicidal activity occurred at low concentrations, ultrastructural alterations and melanin production were observed. The activity of C7a in vitro and in vivo against Candida spp. was analyzed. The results showed fungicidal activity at low values. Also, it was revealed that inhibition of formation of hyphae/pseudohyphae and morphological alterations. In vivo assays demonstrated a significant decrease of fungal border of intravaginal and intravenous infected mice.

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Publishing Date

2018-12-04

Derived works

WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.

BORGES, T. S., et al. Erratum to: Isolation of Sporothrix schenckii From the Claws of Domestic Cats (Indoor and Outdoor) and in Captivity in São Paulo (Brazil) [doi:10.1007/s11046-013-9680-x]. Mycopathologia (1975. Print) [online], 2013, p. 129-137.
Rossi, Diego C, et al. Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesiana in the control of experimental candidiasis [doi:10.1186/1471-2180-12-28]. BMC Microbiology [online], 2012, vol. 12, p. 28.
ROSSI, D. C. P., et al. Eficácia dos taninos condensados extraídos de Stryphnodendron adstringes no tratamento de candidíase vaginal experimental. In 27 Congresso Brasileiro de Microbiologia, Natal - RN, 2013. 27 Congresso Brasileiro de Microbiologia., 2013. Resumo.
ROSSI, D. C. P., et al. Therapeutic study of gomesin in mice infected with Candida albicans. In X International Congress on Paracoccidioidomycosis, medellín, Colômbia, 2008. Biomedica., 2008. Abstract.
SILVA, F. D., et al. Effects of microplusin, a copper chelating antimicrobial peptide against Cryptococcus neoformans. In 25 Congresso Brasileiro de Microbiologia, Porto de Galinhas, 2009. 25 Congresso Brasileiro de Microbiologia., 2009. Resumo.