title: Enhancement of the antimicrobial activity and selectivity of GNU7 against Gram-negative bacteria by fusion with LPS-targeting peptide.
abstract: Antimicrobial peptides (AMPs) provide a potential source of new antimicrobial therapeutics for the treatment of multidrug-resistant pathogens. To develop Gram-negative selective AMPs that can inhibit the effects of lipopolysaccharide (LPS)-induced sepsis, we added various rationally designed LPS-targeting peptides [amino acids 28-34 of lactoferrin (Lf28-34), amino acids 84-99 of bactericidal/permeability increasing protein (BPI84-99), and de novo peptide (Syn)] to the potent AMP, GNU7 (RLLRPLLQLLKQKLR). Compared to our original starting peptide GNU7, hybrid peptides had an 8- to 32-fold improvement in antimicrobial activity against Gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium. Among them, Syn-GNU7 showed the strongest LPS-binding and -neutralizing activities, thus allowing it to selectively eliminate Gram-negative bacteria from within mixed cultures. Our results suggest that LPS-targeting peptides would be useful to increase the antimicrobial activity and selectivity of other AMPs against Gram-negative bacteria.
authors.affiliation: Division of Life Science, Gyeongsang National University, Jinju 52828, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Research Institute of Life Science, Gyeongsang National University, Jinju 52828, South Korea.
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Division of Life Science, Gyeongsang National University, Jinju 52828, South Korea; Research Institute of Life Science, Gyeongsang National University, Jinju 52828, South Korea. Electronic address: juhyun.cho@gnu.ac.kr.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Cho
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000472:pathogenicity; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000472:pathogenicity; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D010455:Peptides
keywords: Antimicrobial peptide; Gram-negative bacteria selectivity; Hybrid peptide; LPS-binding and -neutralizing activities