title: Short Synthetic β-Sheet Antimicrobial Peptides for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Burn Wound Infections.
abstract: Pseudomonas aeruginosa is often implicated in burn wound infections; its inherent drug resistance often renders these infections extremely challenging to treat. This is further compounded by the problem of emerging drug resistance and the dearth of novel antimicrobial drug discovery in recent years. In the perennial search for effective antimicrobial compounds, the authors identify short synthetic β-sheet folding peptides, IRIKIRIK (IK8L), IRIkIrIK (IK8-2D), and irikirik (IK8D) as prime candidates owing to their high potency against Gram-negative bacteria. In this study, the peptides are first assayed against 20 clinically isolated multidrug-resistant P. aeruginosa strains in comparison with the conventional antibiotics imipenem and ceftazidime, and IK8L is demonstrated to be the most effective. IK8L also exhibits superior antibacterial killing kinetics compared to imipenem and ceftazidime. From transmission electron microscopy, confocal microscopy, and protein release analyses, IK8L shows membrane-lytic antimicrobial mechanism. Repeated use of IK8L does not induce drug resistance, while the bacteria develop resistance against the antibiotics after several times of treatment at sublethal doses. Analysis of mouse blood serum chemistry reveals that peptide does not induce systemic toxicity. The potential utility of IK8L in the in vivo treatment of P. aeruginosa-infected burn wounds is further demonstrated in a mouse model.
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Guansheng
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Junchi
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Zhen Chang
authors.initials: ZC
authors.lastname: Liang
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Weiyang
authors.initials: W
authors.lastname: Lou
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Bao
authors.affiliation: School of Physics and Astronomy and Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Zhan Yuin
authors.initials: ZY
authors.lastname: Ong
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
authors.affiliation: Program of Innovative Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D017433:Protein Structure, Secondary; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D014946:Wound Infection / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides
keywords: antimicrobial; burn wounds; infections; multidrug resistance; peptides