02917nas 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-002489nas a2200277   4500008004100000022001400041245016500055210006900220260006700289300001000356490000800366520147900374653001401853653002101867653001501888653001501903653001901918653002801937100001701965700002101982700001602003700001702019700002102036700002602057856012802083       2015                        eng d  a1364-507200aPossible mechanism of antifungal phenazine-1-carboxamide from pseudomonas sp against dimorphic fungi Benjaminiella poitrasii and human pathogen Candida albicans0 aPossible mechanism of antifungal phenazine1carboxamide from pseu  a111 RIVER ST, HOBOKEN 07030-5774, NJ USAbWILEY-BLACKWELLcJAN  a39-480 v1183 a<p>AimInvestigation of antifungal mechanism of phenazine 1-carboxamide (PC) produced by a Pseudomonas strain MCC2142. Methods and ResultsAn antifungal metabolite produced by a Pseudomonas was purified and identified as PC. Human pathogenic fungi such as Candida albicans, Candidaglabrata, Cryptococcus neoformans, Fusarium oxysporum, Aspergillus fumigatus and Aspergillus niger were found to be inhibited by PC (MIC90 32-64gml(-1)). Addition of PC (20gml(-1)) during yeast (Y)-hypha (H) transitions inhibited germ tube formation by &gt;90% and &gt;99% in C.albicans National Collection of Industrial Microorganisms (NCIM) 3471 and nonpathogenic model Benjaminiella poitrasii, respectively. After exposure to PC (20gml(-1)), 75-80% yeast cells of B.poitrasii and C.albicans NCIM 3471 showed rhodamine 123 fluorescence indicating high intracellular reactive oxygen species (ROS) production. ROS further led to hyperpolarization of mitochondrial membrane, subsequently induction of apoptosis as evident by externalization of phosphatidylserine, DNA fragmentation, chromatin condensation and finally death in B.poitrasii. In C.albicans NCIM 3471, PC (20gml(-1)) induced apoptosis. ConclusionsThe antifungal effect of PC in B.poitrasii and C.albicans may be due to ROS-mediated apoptotic death. Significance and Impact of the StudyInhibition of Y-H transition of B.poitrasii and C.albicans by PC indicates that it may prove useful in the control of dimorphic human pathogens.</p>10aApoptosis10aCandida albicans10adimorphism10aphenazines10aPseudomonas sp10areactive oxygen species1 aTupe, S., G.1 aKulkarni, R., R.1 aShirazi, F.1 aSant, D., G.1 aJoshi, Swati, P.1 aDeshpande, Mukund, V.  uhttps://library.ncl.res.in/content/possible-mechanism-antifungal-phenazine-1-carboxamide-pseudomonas-sp-against-dimorphic-0