Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/24841
Title: HIV Aspartic Peptidase Inhibitors Modulate Surface Molecules and Enzyme Activities Involved with Physiopathological Events in Fonsecaea pedrosoi
Authors: Palmeira, Vanila F.
Alviano, Daniela S.
Silva, Lys A. Braga
Goulart, Fátima R. V.
Granato, Marcela Q.
Rozental, Sonia
Alviano, Celuta S.
Santos, André L. S.
Kneipp, Lucimar F.
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Estrutura de Microrganismos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Estrutura de Microrganismos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro,. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil
Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Estrutura de Microrganismos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Biologia Celular de Fungos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Departamento de Microbiologia Geral. Laboratório de Estrutura de Microrganismos. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases.. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro,. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ. Brasil.
Abstract: Fonsecaea pedrosoi is the main etiological agent of chromoblastomycosis, a recalcitrant disease that is extremely difficult to treat. Therefore, new chemotherapeutics to combat this fungal infection are urgently needed. Although aspartic peptidase inhibitors (PIs) currently used in the treatment of human immunodeficiency virus (HIV) have shown anti-F. pedrosoiactivity their exact mechanisms of action have not been elucidated. In the present study, we have investigated the effects of four HIV-PIs on crucial virulence attributes expressed byF. pedrosoiconidial cells, including surface molecules and secreted enzymes, both of which are directly involved in the disease development. In all the experiments, conidia were treated with indinavir, nelfinavir, ritonavir and saquinavir (100 μM) for 24 h, and then fungal cells were used to evaluate the effects of HIV-PIs on different virulence attributes expressed byF. pedrosoi. In comparison to untreated controls, exposure ofF. pedrosoicells to HIV-PIs caused (i) reduction on the conidial granularity; (ii) irreversible surface ultrastructural alterations, such as shedding of electron dense and amorphous material from the cell wall, undulations/invaginations of the plasma membrane with and withdrawal of this membrane from the cell wall; (iii) a decrease in both mannose-rich glycoconjugates and melanin molecules and an increase in glucosylceramides on the conidial surface; (iv) inhibition of ergosterol and lanosterol production; (v) reduction in the secretion of aspartic peptidase, esterase and phospholipase; (vi) significant reduction in the viability of non-pigmented conidia compared to pigmented ones. In summary, HIV-PIs are efficient drugs with an ability to block crucial biological processes ofF. pedrosoiand can be seriously considered as potential compounds for the development of new chromoblastomycosis chemotherapeutics.
Keywords: chromoblastomycosis
Fonsecaea pedrosoi
peptidases
HIV aspartic peptidase inhibitors
antifungal action
keywords: Cromoblastomicose
Peptídeo Hidrolases
ação antifúngica
Inibidores de peptidase aspártica por HIV
Issue Date: 2017
Publisher: Frontiers Media
Citation: PALMEIRA, Vanila F. et al. HIV Aspartic Peptidase Inhibitors Modulate Surface Molecules and Enzyme Activities Involved with Physiopathological Events in Fonsecaea pedrosoi. Frontiers in Microbiology, v.8, Article 918, 12p, May 2017.
DOI: 10.3389/fmicb.2017.00918
ISSN: 1664-302X
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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