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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. [ABSTRACT FROM AUTHOR]

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed. Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. The doubling time was also drastically affected, going from 2.8 h to 22.5 h, which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cytotoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the potential mechanisms of A. occidentale against C. albicans on a cellular level, and might provide a promising option for the design of a new treatment for invasive candidiasis. [ABSTRACT FROM AUTHOR]

Plant-derived compounds have proven to be a source of inspiration for new drugs. In this study, piperine isolated from the fruits of Piper nigrum showed anti-Candida activity. Furthermore, the mechanisms of action of piperine and its impact on virulence factors in Candida albicans, which have not been comprehensively understood, were also assessed. Initially, piperine suppressed the hyphal transition in both liquid and solid media, hindered biofilm formation, and resulted in observable cell distortions in scanning electron microscope (SEM) samples, for both fluconazole-sensitive and fluconazole-resistant C. albicans strains. Additionally, the morphogenetic switches triggered by piperine were found to rely on the activity of mutant C. albicans strains. Secondly, piperine treatment increased cell membrane permeability and disrupted mitochondrial membrane potential, as evidenced by propidium iodine and Rhodamine 123 staining, respectively. Moreover, it induced the accumulation of intracellular reactive oxygen species in C. albicans. Synergy was obtained between the piperine and the fluconazole against the fluconazole-sensitive strain. Interestingly, there were no hemolytic effects of piperine, and it resulted in reduced cytotoxicity on fibroblast cells at low concentrations. The results suggest that piperine could have a dual mode of action inhibiting virulence factors and modulating cellular processes, leading to cell death in C. albicans. [ABSTRACT FROM AUTHOR]

Palindromic peptide LfcinB (21–25)Pal: RWQWRWQWR was synthesized by Solid Phase Peptide Synthesis (SPPS‐Fmoc/tBu), purified by Reverse Phase Solid Phase Extraction (RP‐SPE) and characterized by Reverse Phase High Performance Liquid Chromatography (RP‐HPLC) and Matrix‐Assisted Laser Desorption/Ionization‐Time Of Flight Mass Spectrometry (MALDI‐TOF MS). The antifungal activity of LfcinB (21–25)Pal against both ATCC strains and clinical isolates of C. albicans, C. glabrata, C. krusei, C. auris and C. tropicalis was evaluated. The palindromic peptide exhibited fungistatic and fungicidal activity against all yeast evaluated. The antifungal activity was dependent on peptide concentration in all cases. Additionally, LfcinB (21–25)Pal (25–50 μg/mL) combined with fluconazole exhibited a synergistic antifungal effect against C. tropicalis 883 and C. krusei 6258 (resistant to fluconazole). This study showed that the palindromic peptide derived from Lactoferricin B (LfcinB) exhibited significant antifungal activity against Candida spp, suggesting that this peptide could have a therapeutic application solely or in combination with fluconazole. [ABSTRACT FROM AUTHOR]

Peptides containing the sequences 20 RRWQWR 25 and 20 RRWQWRMKKLG 30 derived from Bovine lactoferricin (LfcinB) were synthesized and their antibacterial effect against reference strains and sensitive and resistant clinical isolates of E. coli was evaluated. Tetra-branched multiple antigen peptide (MAP) ((RRWQWR) 2 -K-Ahx-C) 2 exhibited significant antibacterial activity against sensitive, resistant, and multidrug-resistant clinical isolates of E. coli. Peptide 3: RRWQWR-Nal-KKLG; MIC=16 μM, 26 [F]: (RRWQWRFKKLG) 2 -K-Ahx; MIC=15 μM, 17: (RRWQWRFK) 2 -K-Ahx; MIC=9 μM, and LfcinB (20-25) 2 : (RRWQWR) 2 -K-Ahx; MIC=11 μM exhibited the highest antibacterial activity against E. coli strains, with bactericidal effect and haemolytic effect at MIC less than 5 % and a therapeutic index >1. A synergistic effect of peptides 26 [F] and 17 with ciprofloxacin (CIP) or ceftriaxone (CEF) was observed. Prolonged treatment of E. coli ATCC 25922 with sublethal concentrations of CIP induced resistance in this strain, whereas some peptides did not induce resistance. These peptides can be considered to be promising candidates for treating infections caused by resistant strains of E. coli., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The dimeric peptide 26 [F]: (RRWQWR F KKLG) 2 -K-Ahx has exhibited a potent cytotoxic effect against breast cancer cell lines, with position 26 (F) being the most relevant for anti-cancer activity. In this investigation, six analogues of the 26 [F] peptide were synthesized in which the 26th position was replaced by non-natural hydrophobic amino acids, finding that some modifications increased the resistance to proteolytic degradation exerted by trypsin or pepsin. Additionally, these modifications increased the cytotoxic effect against breast cancer cells and generated cell death mediated by apoptosis pathways, activating caspases 8 and 9, and did not compromise the integrity of the cytoplasmic membrane. Finally, it was found that the modified peptides have a broad spectrum of action, since they also have a cytotoxic effect against the HeLa human cervical cancer cell line. Peptide 26 [F] was inoculated in mice by ip administration and the lethal dose 50 (LD 50 ) was between 70 and 140 mg kg -1 . While for the 26 [1-Nal]: (RRWQWR-1-Nal-KKLG) 2 -K-Ahx peptide, a dose-response test was performed, and the survival rate was 100%. These results suggested that these peptides are safe in this animal model and could be considered as promissory to develop a treatment against breast cancer., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)