title: In vitro and in vivo antibacterial evaluation and mechanistic study of ornithine based small cationic lipopeptides against antibiotic resistant clinical isolates.
abstract: We investigated the in vitro activities of short lipopeptides against a large panel of clinical isolates of antibiotic resistant bacteria. In the animal model, LP16 (5 mg/kg) significantly decreased the burden of viable colony forming unit (CFU) of bacteria. MTT assay results revealed the high selectivity of lipopeptides toward microbial cells. Calcein dye leakage experiments and flow cytometric analysis suggests the membranolytic effect of lipopeptides, which was further confirmed by visualizing bacterial damage via electron microscopy tool (SEM & TEM). Moreover, stability in human blood plasma and no sign of resistance development against clinical isolates of Escherichia coli and Staphylococcus aureus were observed for lead lipopeptides. These results demonstrate the potential of short lipopeptides as a novel class of anti-infectives.
authors: Department of Pharmacy, Jaypee University of Information Technology, Solan 173234, India.
authors: Sandeep
authors: S
authors: Lohan
authors: Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors: Jitender
authors: J
authors: Monga
authors: Environmental Biotechnology & Microbial Biochemistry, Institute of Microbial Technology, Chandigarh 160036, India.
authors: Swaranjit Singh
authors: SS
authors: Cameotra
authors: Department of Pharmacy, Jaypee University of Information Technology, Solan 173234, India. Electronic address: bishtchem2005@gmail.com.
authors: Gopal Singh
authors: GS
authors: Bisht
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009952:Ornithine / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009952:Ornithine
keywords: Antibacterial activity; Antibiotic resistance; Lipopeptides; Membrane active; Plasma stability