title: Two hits are better than one: membrane-active and DNA binding-related double-action mechanism of NK-18, a novel antimicrobial peptide derived from mammalian NK-lysin.
abstract: The extensive use and misuse of antibiotics in medicine result in the emergence of multidrug-resistant bacteria, creating an urgent need for the development of new chemotherapeutic agents. Nowadays, antimicrobial peptides are widely recognized as a class of promising candidates with activity against multidrug-resistant bacteria. NK-18 is a truncated peptide derived from NK-Lysin, an effector of cytotoxic T cells and natural killer cells. In this study, we studied the antibacterial mechanism of action of NK-18. The results revealed that NK-18 has potent antibacterial activity against Escherichia coli and Staphylococcus aureus. According to our findings, NK-18 is membrane active and its target of action is not only the bacterial membrane but also the DNA in the cytoplasm. The double targets of NK-18 make it difficult for bacteria to generate resistance, which may present a new strategy to defend against multidrug-resistant bacteria and provide a new lead in the design of potent antimicrobial peptides with therapeutic application in the presence of increasing resistance to conventional antibiotics.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu Province, People's Republic of China.
authors.forename: Jiexi
authors.initials: J
authors.lastname: Yan
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Dang
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.forename: Junqiu
authors.initials: J
authors.lastname: Xie
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Song
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D011510:Proteolipids / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D053835:Unilamellar Liposomes / Q000032:analysis / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C571367:NK-18 peptide; C093238:NK-lysin; D011510:Proteolipids; D053835:Unilamellar Liposomes; D004247:DNA