Effects of Argentilactone on the Transcriptional Profile, Cell Wall and Oxidative Stress of Paracoccidioides spp

Paracoccidioides spp., a dimorphic pathogenic fungus, is the etiologic agent of paracoccidioidomycosis (PCM). PCM is an endemic disease that affects at least 10 million people in Latin America, causing severe public health problems. The drugs used against pathogenic fungi have various side effects a...

Full description

Saved in:
Bibliographic Details
Published in:PLoS neglected tropical diseases 2016-01, Vol.10 (1), p.e0004309-e0004309
Main Authors: Araújo, Felipe Souto, Coelho, Luciene Melo, Silva, Lívia do Carmo, da Silva Neto, Benedito Rodrigues, Parente-Rocha, Juliana Alves, Bailão, Alexandre Melo, de Oliveira, Cecília Maria Alves, Fernandes, Gabriel da Rocha, Hernández, Orville, Ochoa, Juan Guillermo McEwen, Soares, Célia Maria de Almeida, Pereira, Maristela
Format: Article
Language:English
Subjects:
Antifungal Agents - isolation & purification
Antifungal Agents - metabolism
Ascomycota
Biosynthesis
Cell Wall - drug effects
Drugs
Experiments
Fungal infections
Fungi
Gene expression
Gene Expression Profiling
Genetic aspects
Genetic transcription
Hyptis - chemistry
Lactones
Lactones - isolation & purification
Lactones - metabolism
Mortality
Observations
Oxidative Stress
Paracoccidioides - drug effects
Paracoccidioides - genetics
Paracoccidioides - growth & development
Properties
Public health
Real-Time Polymerase Chain Reaction
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Paracoccidioides spp., a dimorphic pathogenic fungus, is the etiologic agent of paracoccidioidomycosis (PCM). PCM is an endemic disease that affects at least 10 million people in Latin America, causing severe public health problems. The drugs used against pathogenic fungi have various side effects and limited efficacy; therefore, there is an inevitable and urgent medical need for the development of new antifungal drugs. In the present study, we evaluated the transcriptional profile of Paracoccidioides lutzii exposed to argentilactone, a constituent of the essential oil of Hyptis ovalifolia. A total of 1,058 genes were identified, of which 208 were up-regulated and 850 were down-regulated. Cell rescue, defense and virulence, with a total of 26 genes, was a functional category with a large number of genes induced, including heat shock protein 90 (hsp90), cytochrome c peroxidase (ccp), the hemoglobin ligand RBT5 (rbt5) and superoxide dismutase (sod). Quantitative real-time PCR revealed an increase in the expression level of all of those genes. An enzymatic assay showed a significant increase in SOD activity. The reduced growth of Pbhsp90-aRNA, Pbccp-aRNA, Pbsod-aRNA and Pbrbt5-aRNA isolates in the presence of argentilactone indicates the importance of these genes in the response of Paracoccidioides spp. to argentilactone. The response of the P. lutzii cell wall to argentilactone treatment was also evaluated. The results showed that argentilactone caused a decrease in the levels of polymers in the cell wall. These results suggest that argentilactone is a potential candidate for antifungal therapy.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0004309