title: High cell selectivity and low-level antibacterial resistance of designed amphiphilic peptide G(IIKK)(3)I-NH(2).
abstract: On the basis of cell cultures involving bacterial strains (Escherichia coli 5α and Bacillus subtilis 168) and a mammalian cell line (NIH 3T3), the potent antibacterial activity and distinct selectivity from designed amphiphilic peptides G(IIKK)nI-NH2 (n = 2-4) have been demonstrated. This work extends these studies to multidrug resistant pathogens (ESBL-producing E. coli) and primary human cells (HDFa), followed by the in vivo mouse model investigation of ESBL-producing bacterial infection. G(IIKK)3I-NH2 exhibits high antibacterial activity against the pathogenic strain both in vitro and in vivo while displaying low toxicity toward the primary cells and the mice. Peptide molecules can kill bacteria by selectively interacting with bacterial membranes, causing structural disruptions. Furthermore, multidrug resistant ESBL-producing bacteria do not develop resistance after multiple treatments with G(IIKK)3I-NH2. The high cellular selectivity, low toxicity toward mammalian hosts and noninducing bacterial resistance indicate great potential for developing the peptides as anti-infection agents.
authors.affiliation: Centre for Bioengineering and Biotechnology, China University of Petroleum (East China) , 66 Changjiang West Road, Qingdao 266580, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.forename: Yucan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001412:Bacillus subtilis / Q000187:drug effects / Q000648:ultrastructure; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary
chemical_list: D000900:Anti-Bacterial Agents; C000602302:G(IIKK)3I-NH2; D008070:Lipopolysaccharides; D010455:Peptides
keywords: ESBL-producing E. coli infection; antimicrobial peptide; cell selectivity; drug resistance; helical peptide; membrane disruption