PbGP43 Genotyping Using Paraffin-Embedded Biopsies of Human Paracoccidioidomycosis Reveals a Genetically Distinct Lineage in the Paracoccidioides brasiliensis Complex

Abstract Paracoccidioidomycosis (PCM) is a systemic mycosis caused by a group of cryptic species embedded in the Paracoccidioides brasiliensis complex and Paracoccidioides lutzii. Four species were recently inferred to belong to the P. brasiliensis complex, but the high genetic diversity found in both human and environmental samples have suggested that the number of lineages may be higher.This study aimed to assess the 43-kilodalton glycoprotein genotypes (PbGP43) in paraffin-embedded samples from PCM patients to infer the phylogenetic lineages of the P. brasiliensis complex responsible for causing the infection.Formalin-fixed, paraffin-embedded (FFPE) tissue samples from patients with histopathological diagnosis of PCM were analyzed. DNAs were extracted and amplified for a region of the second exon of the PbGP43 gene. Products were sequenced and aligned with other PbGP43 sequences available. A haplotype network and the phylogenetic relationships among sequences were inferred. Amino acid substitutions were investigated regarding the potential to modify physicochemical properties in the proteins.Six phylogenetic lineages were identified as belonging to the P. brasiliensis complex. Two lineages did not group with any of the four recognized species of the complex, and, interestingly, one of them comprised only FFPE samples. A coinfection involving two lineages was found. Five parsimony-informative sites were identified and three of them showed radical non-synonymous substitutions with the potential to promote changes in the protein.This study expands the knowledge regarding the genetic diversity existing in the P. brasiliensis complex and shows the potential of FFPE samples in species identification and in detecting coinfections.

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Identification, N-terminal region sequencing and similarity analysis of differentially expressed proteins in Paracoccidioides brasiliensis

Medical Mycology ◽

10.1046/j.1365-280x.1999.00211.x ◽

1999 ◽

Vol 37 (2) ◽

pp. 115-121 ◽

Cited By ~ 2

Author(s):

A. F. Cunha ◽

M. V. Sousa ◽

S. P. Silva ◽

R. S. A. JesuIno ◽

C. M. A. Soares ◽

...

Keyword(s):

Paracoccidioides Brasiliensis ◽

Terminal Region ◽

Differentially Expressed ◽

Similarity Analysis ◽

Differentially Expressed Proteins

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Updates and comparative analysis of the mitochondrial genome of Paracoccidioides brasiliensis (Pb18) and Paracoccidioides americana (Pb03) using Oxford-Nanopore MinION sequencing

10.26226/morressier.5ac39997d462b8028d89a215 ◽

2018 ◽

Author(s):

OLIVER K. Clay

Keyword(s):

Comparative Analysis ◽

Mitochondrial Genome ◽

Paracoccidioides Brasiliensis ◽

Oxford Nanopore

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Recognition of Fungal Components by the Host Immune System

Current Protein and Peptide Science ◽

10.2174/1389203721666191231105546 ◽

2020 ◽

Vol 21 (3) ◽

pp. 245-264 ◽

Cited By ~ 3

Author(s):

Laura C. García-Carnero ◽

José A. Martínez-Álvarez ◽

Luis M. Salazar-García ◽

Nancy E. Lozoya-Pérez ◽

Sandra E. González-Hernández ◽

...

Keyword(s):

Immune System ◽

Histoplasma Capsulatum ◽

Paracoccidioides Brasiliensis ◽

Sporothrix Schenckii ◽

Clinical Importance ◽

Pathogenic Fungi ◽

Diagnostic Tools ◽

Future Research ◽

Host Immune System ◽

Fungal Antigens

: 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.

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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

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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

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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.

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