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New lipopeptide homologues (AF3, AF4 and AF5) with antifungal activities against Candida and Cryptococcus spp. were purified from the cell free supernatant of Bacillus subtilis RLID 12.1. The lipopeptides AF3, AF4 and AF5 were identified with the same peptide sequence Asn-Pro-Tyr-Asn-Gln-Thr-Ser with variations in the fatty acid branching type and chain length (anteiso-C17, iso-C17 and iso-C18 respectively). Comparing the three homologues for minimum inhibitory concentrations (MIC) against 81 Candida (64 no.) and Cryptococcus (17 no.) clinical isolates and its cytotoxicity, AF4 was found as the most promising antifungal lipopeptide which exhibited MICg of 3.31, 3.41, 3.48 and 2.83 μg/mL showing 100% inhibition against Candida albicans, Candida tropicalis, Candida auris and Cryptococcus neoformans respectively with low hemolysis value (<6%) and IC50 values (13.31 μg/mL). The additive effects among the homologues AF3, AF4 and AF5 were evaluated against 3 Candida species along with the cytotoxicity studies. Five combinations exhibited good additive interaction effects: AF3, AF4 (4, 4 μg/mL), AF3, AF5 (4, 4 μg/mL), AF3, AF5 (2, 4 μg/mL) AF4, AF5 (4, 4 μg/mL) and AF4, AF5 (2, 4 μg/mL) in planktonic cell inhibition and AF3, AF4 (4, 4 μg/mL), AF3, AF5 (4, 4 μg/mL) and AF3, AF5 (2, 4 μg/mL) in the inhibition of biofilm formation. However the combinations (AF3, AF4) and (AF3, AF5) showing >70% cell survival with low hemolysis (<5%) were found to be comparatively effective. To date this is the first study which describes the additive effects of lipopeptide homologues showing reduced cytotoxicity against mammalian cells and the combination might serve as a potent anti-biofilm forming substitute. Copyright © 2017 American Society for Microbiology.


Ramya R, Manjari Shrivastava, Namitha N N, Ram Lal Thakur, Arunaloke Chakrabarti, Utpal Roy. Evaluation of Antifungal efficacy of three new cyclic lipopeptides of the class Bacillomycin from Bacillus subtilis RLID 12.1. Antimicrobial agents and chemotherapy. 2017 Oct 16

PMID: 29038271

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