Antifungal Synergy: Mechanistic Insights into the R-1-R Peptide and Bidens pilosa Extract as Potent Therapeutics against Candida spp. through Proteomics.
Yerly Vargas-CasanovaClaudia Patricia Bravo-ChaucanésSamuel de la Cámara FuentesRaquel Martinez-LopezLucia MonteolivaConcha GilZuly Jenny RiveraGeison Modesti CostaJavier Eduardo García CastañedaClaudia Marcela Parra-GiraldoPublished in: International journal of molecular sciences (2024)
Previous reports have demonstrated that the peptide derived from LfcinB, R-1-R, exhibits anti- Candida activity, which is enhanced when combined with an extract from the Bidens pilosa plant. However, the mechanism of action remains unexplored. In this research, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both the SC5314 strain and a fluconazole-resistant isolate of Candida albicans after incubation with R-1-R. The proteomic data revealed that treatment with R-1-R led to the up-regulation of most differentially expressed proteins compared to the controls in both strains. These proteins are primarily involved in membrane and cell wall biosynthesis, membrane transport, oxidative stress response, the mitochondrial respiratory chain, and DNA damage response. Additionally, proteomic analysis of the C. albicans parental strain SC5314 treated with R-1-R combined with an ethanolic extract of B. pilosa was performed. The differentially expressed proteins following this combined treatment were involved in similar functional processes as those treated with the R-1-R peptide alone but were mostly down-regulated (data are available through ProteomeXchange with identifier PXD053558). Biological assays validated the proteomic results, evidencing cell surface damage, reactive oxygen species generation, and decreased mitochondrial membrane potential. These findings provide insights into the complex antifungal mechanisms of the R-1-R peptide and its combination with the B. pilosa extract, potentially informing future studies on natural product derivatives.
Keyphrases
- candida albicans
- oxidative stress
- biofilm formation
- cell wall
- label free
- dna damage response
- reactive oxygen species
- anti inflammatory
- electronic health record
- escherichia coli
- big data
- small molecule
- high throughput
- mass spectrometry
- emergency department
- machine learning
- dna repair
- transcription factor
- climate change
- current status
- single cell
- artificial intelligence
- cystic fibrosis
- replacement therapy
- case control