Paracoccidioides brasiliensis, Paracoccidioidomycosis, and Antifungal Antibiotics

: By being the first point of contact of the fungus with the host, the cell wall plays an important role in the pathogenesis, having many molecules that participate as antigens that are recognized by immune cells, and also that help the fungus to establish infection. The main molecules reported to trigger an immune response are chitin, glucans, oligosaccharides, proteins, melanin, phospholipids, and others, being present in the principal pathogenic fungi with clinical importance worldwide, such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Blastomyces dermatitidis, and Sporothrix schenckii. Knowledge and understanding of how the immune system recognizes and responds to fungal antigens are relevant for the future research and development of new diagnostic tools and treatments for the control of mycosis caused by these fungi.

Download Full-text

Design and synthesis of new antifungals based on N- un-substituted azoles as 14α demethylase inhibitor

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200217090855 ◽

2020 ◽

Vol 16 ◽

Author(s):

Asghar Davood ◽

Aneseh Rahimi ◽

Maryam Iman ◽

Parisa Azerang ◽

Soroush Sardari ◽

...

Keyword(s):

Antimicrobial Agents ◽

Antifungal Agents ◽

Molecular Design ◽

Pathogenic Fungi ◽

Antimicrobial Activities ◽

Docking Studies ◽

Receptor Interaction ◽

Main Role ◽

Design And Synthesis ◽

Antifungal Antibiotics

Objective(s): Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are N-substituted azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole antifungals. Due to importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole) in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted azoles in which both of nitrogen is un-substituted was reported. Materials and Methods: Designed compounds were synthesized by reaction of imidazole-4-carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae were done using a broth micro-dilution assay. Docking studies were done using AutoDock. Results: Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial activities against tested pathogenic fungi, wherein compound 3, 7 and 8 were potent. Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azole-heme coordination play main role in drug-receptor interaction. Conclusion: Our results offer some useful references in order to molecular design performance or modification of this series of compounds as a lead compound to discover new and potent antimicrobial agents.

Download Full-text

Metabolic Peculiarities of Paracoccidioides brasiliensis Dimorphism as Demonstrated by iTRAQ Labeling Proteomics

Frontiers in Microbiology ◽

10.3389/fmicb.2019.00555 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 7

Author(s):

Danielle Silva Araújo ◽

Maristela Pereira ◽

Igor Godinho Portis ◽

Agenor de Castro Moreira dos Santos Junior ◽

Wagner Fontes ◽

...

Keyword(s):

Paracoccidioides Brasiliensis ◽

Itraq Labeling

Download Full-text

Brazilian Red Propolis shows antifungal and immunomodulatory activities against Paracoccidioides brasiliensis

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114181 ◽

2021 ◽

pp. 114181

Author(s):

Lauana Aparecida Santos ◽

Pedro Luiz Rosalen ◽

Nayara Andrade Dias ◽

Julianne Caravita Grisolia ◽

Bruno José Nascimento Gomes ◽

...

Keyword(s):

Paracoccidioides Brasiliensis

Download Full-text

Protective Response in Experimental Paracoccidioidomycosis Elicited by Extracellular Vesicles Containing Antigens of Paracoccidioides brasiliensis

Cells ◽

10.3390/cells10071813 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1813

Author(s):

Ludmila Matos Baltazar ◽

Gabriela Fior Ribeiro ◽

Gustavo J. Freitas ◽

Celso Martins Queiroz-Junior ◽

Caio Tavares Fagundes ◽

...

Keyword(s):

Extracellular Vesicles ◽

Treatment Effectiveness ◽

Ex Vivo ◽

Paracoccidioides Brasiliensis ◽

Systemic Disease ◽

Host Immune System ◽

Antigen Delivery ◽

Activated T Lymphocytes ◽

Cell Mobilization

Paracoccidioidomycosis (PCM) is a systemic disease caused by Paracoccidioides spp. PCM is endemic in Latin America and most cases are registered in Brazil. This mycosis affects mainly the lungs, but can also spread to other tissues and organs, including the liver. Several approaches have been investigated to improve treatment effectiveness and protection against the disease. Extracellular vesicles (EVs) are good antigen delivery vehicles. The present work aims to investigate the use of EVs derived from Paracoccidioides brasiliensis as an immunization tool in a murine model of PCM. For this, male C57BL/6 were immunized with two doses of EVs plus adjuvant and then infected with P. brasiliensis. EV immunization induced IgM and IgG in vivo and cytokine production by splenocytes ex vivo. Further, immunization with EVs had a positive effect on mice infected with P. brasiliensis, as it induced activated T lymphocytes and NKT cell mobilization to the infected lungs, improved production of proinflammatory cytokines and the histopathological profile, and reduced fungal burden. Therefore, the present study shows a new role for P. brasiliensis EVs in the presence of adjuvant as modulators of the host immune system, suggesting their utility as immunizing agents.

Download Full-text