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: Guoqiu Wu, Xiaobo Fan, Linxian Li, Hailiang Wang, Jiaxuan Ding, Wu Hongbin, Rui Zhao, Lixia Gou, Zilong Shen, Tao Xi
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 35 Issue 3 Pg. 250-4 (Mar 2010) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 20045294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• Antimicrobial Cationic Peptides
• Endotoxins
• Lipopolysaccharides
• Peptides, Cyclic
• thanatin

Topics

• Amino Acid Substitution (genetics)
• Animals
• Antimicrobial Cationic Peptides (metabolism, therapeutic use)
• Ascitic Fluid (microbiology)
• Blood (microbiology)
• Colony Count, Microbial
• Drug Resistance, Multiple, Bacterial
• Endotoxins (blood)
• Escherichia coli (drug effects)
• Escherichia coli Infections (drug therapy)
• Injections, Intraperitoneal
• Lipopolysaccharides (antagonists & inhibitors)
• Male
• Mice
• Mice, Inbred ICR
• Microbial Viability
• Peptides, Cyclic (administration & dosage, genetics, metabolism, therapeutic use)
• Protein Binding
• Shock, Septic (drug therapy)
• Survival Analysis