02567nas a2200289   4500008004100000022001400041245015400055210006900209260007900278300001400357490000700371520150300378653002401881653002101905653001401926653000801940100002701948700001901975700001901994700001702013700002202030700001802052700002602070700002902096700002102125856013102146       2011                        eng d  a0196-978100aAntifungal activity of novel synthetic peptides by accumulation of reactive oxygen species (ROS) and disruption of cell wall against Candida albicans0 aAntifungal activity of novel synthetic peptides by accumulation   a360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USAbELSEVIER SCIENCE INCcAUG  a1732-17400 v323 a<p>In the present work, we investigated the antifungal activity of two de novo designed, antimicrobial peptides VS2 and VS3, incorporating unnatural amino acid alpha,beta-dehydrophenylalanine (Delta Phe). We observed that the low-hemolytic peptides could irreversibly inhibit the growth of various Candida species and multidrug resistance strains at MIC(80) values ranging from 15.62 mu M to 250 mu M. Synergy experiments showed that MIC(80) of the peptides was drastically reduced in combination with an antifungal drug fluconazole. The dye PI uptake assay was used to demonstrate peptide induced cell membrane permeabilization. Intracellular localization of the FITC-labeled peptides in Candida albicans was studied by confocal microscopy and FACS. Killing kinetics, PI uptake assay, and the intracellular presence of FITC-peptides suggested that growth inhibition is not solely a consequence of increased membrane permeabilization. We showed that entry of the peptide in Candida cells resulted in accumulation of reactive oxygen species (ROS) leading to cell necrosis. Morphological alteration in Candida cells caused by the peptides was visualized by electron microscopy. We propose that de novo designed VS2 and VS3 peptides have multiple detrimental effects on target fungi, which ultimately result in cell wall disruption and killing. Therefore, these peptides represent a good template for further design and development as antifungal agents. (C) 2011 Elsevier Inc. All rights reserved.</p>10aAntifungal peptides10aCandida albicans10aCell wall10aROS1 aMaurya, Indresh, Kumar1 aPathak, Sarika1 aSharma, Monika1 aSanwal, Hina1 aChaudhary, Preeti1 aTupe, Santosh1 aDeshpande, Mukund, V.1 aChauhan, Virander, Singh1 aPrasad, Rajendra  uhttps://library.ncl.res.in/content/antifungal-activity-novel-synthetic-peptides-accumulation-reactive-oxygen-species-ros-and-002917nas a2200313   4500008004100000022001400041245008300055210006900138260007300207300001400280490000900294520181400303653002302117653003202140653001402172653002102186653003402207100002702241700002802268700002002296700002502316700002202341700002402363700002602387700002602413700002102439700002902460856011402489       2013                        eng d  a0304-416500aMechanism of action of novel synthetic dodecapeptides against Candida albicans0 aMechanism of action of novel synthetic dodecapeptides against Ca  aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcNOV  a5193-52030 v18303 a<p>Background: Three de novo designed low molecular weight cationic peptides (IJ2, IJ3 and IJ4) containing an unnatural amino acid alpha,beta-didehydrophenylalanine (APhe) exhibited potent antifungal activity against fluconazole (FLC) sensitive and resistant clinical isolates of Candida albicans as well as non-albi cans and other yeast and filamentous pathogenic fungi. In the present study, their synthesis, susceptibility of different fungi and the mechanism of anti-candidal action have been elucidated. Methods: The antimicrobial peptides (AMPs) were synthesized by solid-phase method and checked for antifungal activity against different yeasts and fungi by broth microdilution method. Anti-candidal mode of action of the peptides was investigated through detecting membrane permeabilization by confocal microscopy, Reactive Oxygen Species (ROS) generation by fluorometry, apoptosis and necrosis by flow cytometry and cell wall damage using Scanning and Transmission Electron Microscopy. Results and conclusions: The MIC of the peptides against C. albicans and other yeast and filamentous fungal pathogens ranged between 3.91 and 250 mu M. All three peptides exhibited effect on multiple targets in C. albi cans including disruption of cell wall structures, compromised cell membrane permeability leading to their enhanced entry into the cells, accumulation of ROS and induction of apoptosis. The peptides also showed synergistic effect when used in combination with fluconazole (FLC) and caspofungin (CAS) against C. albi cans. General significance: The study suggests that the AMPs alone or in combination with conventional antifungals hold promise for the control of fungal pathogens, and need to be further explored for treatment of fungal infections. (C) 2013 Elsevier By. All rights reserved.</p>10aAntifungal peptide10aAntimicrobial peptide (AMP)10aApoptosis10aCandida albicans10aReactive Oxygen Species (ROS)1 aMaurya, Indresh, Kumar1 aThota, Chaitanya, Kumar1 aSharma, Jyotsna1 aTupe, Santosh, Genba1 aChaudhary, Preeti1 aSingh, Manoj, Kumar1 aThakur, Indu, Shekhar1 aDeshpande, Mukund, V.1 aPrasad, Rajendra1 aChauhan, Virander, Singh  uhttps://library.ncl.res.in/content/mechanism-action-novel-synthetic-dodecapeptides-against-candida-albicans-0