Evaluation of Antifungal Efficacy of Three New Cyclic Lipopeptides of the Class Bacillomycin from Bacillus subtilis RLID 12.1

• Published in: Antimicrobial agents and chemotherapy Vol. 62; no. 1
• Main Authors: Ramachandran, Ramya, Shrivastava, Manjari, Narayanan, Namitha N, Thakur, Ram Lal, Chakrabarti, Arunaloke, Roy, Utpal
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.01.2018
• Subjects: Antifungal Agents; Bacillus subtilis; Candida; Candida albicans; Candida tropicalis; Cryptococcus neoformans; Lipopeptides; Peptides, Cyclic; Susceptibility; new cyclic lipopeptides; Bacillus subtilis; interaction study; cytotoxicity; biofilm
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.01457-17

New lipopeptide homologues (AF , AF , and AF ) with antifungal activities against and spp. were purified from a cell-free supernatant of RLID 12.1. The lipopeptides AF , AF , and AF 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 ( -C , -C , and -C , respectively). Upon comparing the three homologues for MICs against 81 ( = 64) and ( = 17) clinical isolates and their cytotoxicities, we found that AF was the most promising antifungal lipopeptide, since it demonstrated 100% inhibition at geometric mean MICs of 3.31, 3.41, 3.48, and 2.83 μg/ml against , , , and , respectively, with low hemolysis values (<6%) and 50% inhibitory concentrations (13.31 μg/ml). The additive effects among the homologues AF , AF , and AF were evaluated against three species, along with the cytotoxicity studies. Five combinations exhibited good additive interaction effects: AF /AF (at corresponding concentrations of 4 and 4 μg/ml [4/4 μg/ml]), AF /AF (4/4 μg/ml), AF /AF (2/4 μg/ml), AF /AF (4/4 μg/ml), and AF /AF (2/4 μg/ml) in planktonic cell inhibition and AF /AF (4/4 μg/ml), AF /AF (4/4 μg/ml), and AF /AF (2/4 μg/ml) in the inhibition of biofilm formation. However, combinations AF /AF and AF /AF , which showed >70% cell survival with low hemolysis (<5%), were found to be comparatively effective. We describe here the additive effects of lipopeptide homologues showing reduced cytotoxicity against mammalian cells; these combinations might serve as a potent antibiofilm-forming substitute.