title: Cell penetrating synthetic antimicrobial peptides (SAMPs) exhibiting potent and selective killing of mycobacterium by targeting its DNA.
abstract: Naturally occurring antimicrobial peptides (AMPs) are powerful defence tools to tackle pathogenic microbes. However, limited natural production and high synthetic costs in addition to poor selectivity limit large-scale use of AMPs in clinical settings. Here, we present a series of synthetic AMPs (SAMPs) that exhibit highly selective and potent killing of Mycobacterium (minimum inhibitory concentration <20 μg mL(-1)) over E. coli or mammalian cells. These SAMPs are active against rapidly multiplying as well as growth saturated Mycobacterium cultures. These SAMPs are not membrane-lytic in nature, and are readily internalized by Mycobacterium and mammalian cells; whereas in E. coli, the lipopolysaccharide layer inhibits their cellular uptake, and hence, their antibacterial action. Upon internalization, these SAMPs interact with the unprotected genomic DNA of mycobacteria, and impede DNA-dependent processes, leading to bacterial cell death.
authors.affiliation: Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Indore Bypass Road, Bhauri, Bhopal, 462066 (India).
authors.forename: Aashish
authors.initials: A
authors.lastname: Sharma
authors.forename: Amol Arunrao
authors.initials: AA
authors.lastname: Pohane
authors.forename: Sandhya
authors.initials: S
authors.lastname: Bansal
authors.forename: Avinash
authors.initials: A
authors.lastname: Bajaj
authors.forename: Vikas
authors.initials: V
authors.lastname: Jain
authors.forename: Aasheesh
authors.initials: A
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D057846:Cell-Penetrating Peptides; D008070:Lipopolysaccharides; D010455:Peptides; D004247:DNA
keywords: DNA; antimicrobials; peptides; polyamides; selectivity