The dimorphic fungus Paracoccidioides spp. is responsible for paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America, causing serious public health problems. Adequate treatment of mycotic infections is difficult, since fungi are eukaryotic organisms with a structure and metabolism similar to those of eukaryotic hosts. In this way, specific fungus targets have become important to search of new antifungal compound. The role of the glyoxylate cycle and its enzymes in microbial virulence has been reported in many fungal pathogens, including Paracoccidioides spp. Here, we show the action of argentilactone and its semi-synthetic derivative reduced argentilactone on recombinant and native isocitrate lyase from Paracoccidioides lutzii Pb01 (PbICL) in the presence of different carbon sources, acetate and glucose. Additionally, argentilactone and its semi-synthetic derivative reduced argentilactone exhibited relevant inhibitory activity against P. lutzii Pb01 yeast cells and dose-dependently influenced the transition from the mycelium to yeast phase. The other oxygenated derivatives tested, epoxy argentilactone and diol argentilactone-, did not show inhibitory action on the fungus. The results were supported by in silico experiments.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994062PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094832PLOS

Publication Analysis

Top Keywords

lutzii pb01
12
argentilactone semi-synthetic
12
paracoccidioides lutzii
8
isocitrate lyase
8
paracoccidioides spp
8
semi-synthetic derivative
8
derivative reduced
8
reduced argentilactone
8
argentilactone
6
inhibition paracoccidioides
4

Similar Publications

The pathogen Paracoccidioides lutzii (Pb01) is found in South America countries Colombia, Ecuador, Venezuela and Brazil, especially in the central, west, and north regions of the latter. It belongs to the Ajellomycetaceae family, Onygenales order, and is typically thermodimorphic, presenting yeast cells when it grows in animal tissues, but mycelia when in the environment, where it produces the infectious propagule. This fungus is one of the etiologic agents of Paracoccidioidomycosis (PCM), the most important endemic fungal infection in Latin America.

View Article and Find Full Text PDF

Molecular Phylogenetic Analysis of Species Complex Present in Paracoccidioidomycosis Patient Tissue Samples.

Microorganisms

February 2023

Laboratory of Immunopathology and Infectious Agents-LIAI, UNIPEX-Experimental Research Unity-Sector 5, Medical School of Botucatu, São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil.

Article Synopsis
  • Paracoccidioidomycosis (PCM) is the most common systemic fungal infection in Latin America, previously thought to be caused by a single species, but has since been updated to include multiple cryptic species, including S1, PS2, PS3, and PS4.
  • Researchers at the Hospital of Medical School of Botucatu-UNESP aimed to analyze biopsy samples from PCM patients to understand the distribution of these species in the Botucatu region, an area known for its PCM prevalence.
  • Using molecular techniques like DNA extraction and PCR, they found that 100% of the positive samples corresponded to the S1 species, highlighting its dominance in the São Paulo State region.
View Article and Find Full Text PDF

Differentially expressed proteins in the interaction of Paracoccidioides lutzii with human monocytes.

Rev Iberoam Micol

December 2021

Department of Biological Sciences, Proteomics Laboratory, Biotechnology and Genetics Center, State University of Santa Cruz, Ilhéus, Bahia, Brazil. Electronic address:

Background: Fungi of the genus Paracoccidioides are the etiological agents of paracoccidioidomycosis, a highly prevalent mycosis in Latin America. Infection in humans occurs by the inhalation of conidia, which later revert to the form of yeast. In this context, macrophages are positioned as an important line of defense, assisting in the recognition and presentation of antigens, as well as producing reactive oxygen species that inhibit fungal spreading.

View Article and Find Full Text PDF

Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts.

Mem Inst Oswaldo Cruz

April 2021

Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, Departamento de Análises Clínicas, Laboratório de Micologia Clínica, Araraquara, SP, Brasil.

Article Synopsis
  • Paracoccidioidomycosis (PCM) is a significant fungal infection prevalent in Latin America, caused by species from the Paracoccidioides genus, which can exist in both mycelial and yeast forms.
  • This study utilized quantitative polymerase chain reaction (qPCR) to measure how specific virulence-related genes expressed in these fungal forms change after they interact with alveolar macrophages and fibroblasts.
  • Results indicated a notable increase in the expression of several genes, particularly the 14-3-3 gene, suggesting that these genes are upregulated during interactions with host cells, potentially contributing to the fungi's virulence.
View Article and Find Full Text PDF

Melanin as a Virulence Factor in Different Species of Genus .

J Fungi (Basel)

November 2020

Instituto de Ciencias Biomedicas, Departamento de Microbiologia, Universidade de Sao Paulo, Sao Paulo 05508-000, Brazil.

Paracoccidioidomycosis (PCM) is a granulomatous systemic mycosis caused by the thermo-dimorphic fungi of the genus . Melanin production by fungi can affect their pathogenesis and virulence. This study evaluates the production of melanin by different isolates of genus and examines how the presence of this polymer affects yeast cell phagocytosis, as well as laccase enzyme production.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!