title: Interaction of antimicrobial peptide s-thanatin with lipopolysaccharide in vitro and in an experimental mouse model of septic shock caused by a multidrug-resistant clinical isolate of Escherichia coli.
abstract: s-thanatin, an analogue of thanatin, was synthesised by substituting the fifteenth amino acid threonine with serine and showed broad antimicrobial activity against Gram-negative and Gram-positive bacteria. To evaluate its antimicrobial activity against a multidrug-resistant (MDR) clinical isolate as well as its anti-endotoxin activity, its lipopolysaccharide (LPS)-binding and -neutralising activity in vitro and its therapeutic efficacy in an experimental model of septic shock caused by a MDR clinical isolate of Escherichia coli were studied. The ability of s-thanatin to bind or neutralise LPS from E. coli O111:B4 was determined using a quantitative assay kit. Male ICR mice were given an intraperitoneal (i.p.) administration of 2x10(10) colony-forming units of E. coli E79466. Following bacterial challenge, all animals were randomised to receive i.p. administration of saline, 40mg/kg ceftazidime (CAZ), or 40mg/kg CAZ+s-thanatin (10, 20 or 40mg/kg). The results showed that s-thanatin not only completely bound to the LPS (median effective concentration of 17.5microg/mL) but also improved the survival and reduced the number of inoculated bacteria in a mouse model of septic shock. s-thanatin may be an attractive candidate to develop as an anti-MDR bacterial agent.
authors.affiliation: Center of Clinical Laboratory Medicine of Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing 210009, China. nationball@163.com
authors.forename: Guoqiu
authors.initials: G
authors.lastname: Wu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Fan
authors.forename: Linxian
authors.initials: L
authors.lastname: Li
authors.forename: Hailiang
authors.initials: H
authors.lastname: Wang
authors.forename: Jiaxuan
authors.initials: J
authors.lastname: Ding
authors.forename: Wu
authors.initials: W
authors.lastname: Hongbin
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Lixia
authors.initials: L
authors.lastname: Gou
authors.forename: Zilong
authors.initials: Z
authors.lastname: Shen
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000382:microbiology; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D024901:Drug Resistance, Multiple, Bacterial; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050296:Microbial Viability; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D011485:Protein Binding; D012772:Shock, Septic / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D023181:Antimicrobial Cationic Peptides; D004731:Endotoxins; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; C098076:thanatin