Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant Bacteria In Vitro and in Mouse Models

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 动物活性蛋白多肽组学

	Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant Bacteria In Vitro and in Mouse Models
	Li SA 1,2; Lee WH[]1; Zhang Y[]1
刊名	ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
	2012
卷号	56 期号:6 页码:3309-3317
通讯作者	leewh@mail.kiz.ac.cn ; zhangy@mail.kiz.ac.cn
英文摘要	Antimicrobial peptides (AMPs) have been considered alternatives to conventional antibiotics for drug-resistant bacterial infections. However, their comparatively high toxicity toward eukaryotic cells and poor efficacy in vivo hamper their clinical application. OH-CATH30, a novel cathelicidin peptide deduced from the king cobra, possesses potent antibacterial activity in vitro. The objective of this study is to evaluate the efficacy of OH-CATH30 and its analog OH-CM6 against drug-resistant bacteria in vitro and in vivo. The MICs of OH-CATH30 and OH-CM6 ranged from 1.56 to 12.5 mu g/ml against drug-resistant clinical isolates of several pathogenic species, including Escherichia coil, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The MICs of OH-CATH30 and OH-CM6 were slightly altered in the presence of 25% human serum. OH-CATH30 and OH-CM6 killed E. coli quickly (within 60 min) by disrupting the bacterial cytoplasmic membrane. Importantly, the 50% lethal doses (LD50) of OH-CATH30 and OH-CM6 in mice following intraperitoneal (i.p.) injection were 120 mg/kg of body weight and 100 mg/kg, respectively, and no death was observed at any dose up to 160 mg/kg following subcutaneous (s.c.) injection. Moreover, 10 mg/kg OH-CATH30 or OH-CM6 significantly decreased the bacterial counts as well as the inflammatory response in a mouse thigh infection model and rescued infected mice in a bacteremia model induced by drug-resistant E. coli. Taken together, our findings demonstrate that the natural cathelicidin peptide OH-CATH30 and its analogs exhibit relatively low toxicity and potent efficacy in mouse models, indicating that they may have therapeutic potential against the systemic infections caused by drug-resistant bacteria.
收录类别	SCI
资助信息	This work was supported by grants from the National Natural Science FoundationofChina(NSFC-YunnanjointfundingU1132601,31071926, 30960384),theNationalBasicResearchProgramofChina(973Program, 2010CB529800), and the National Science & Technology Major Project (2009ZX09103-147).
语种	英语
WOS记录号	WOS:000304432800068
公开日期	2012-09-07
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7061]
专题	昆明动物研究所_动物活性蛋白多肽组学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan, China 2.Graduate School of the Chinese Academy of Science, Beijing, China
推荐引用方式 GB/T 7714	Li SA,Lee WH[],Zhang Y[]. Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant Bacteria In Vitro and in Mouse Models[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,2012,56(6):3309-3317.
APA	Li SA,Lee WH[],&Zhang Y[].(2012).Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant Bacteria In Vitro and in Mouse Models.ANTIMICROBIAL AGENTS AND CHEMOTHERAPY,56(6),3309-3317.
MLA	Li SA,et al."Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant Bacteria In Vitro and in Mouse Models".ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 56.6(2012):3309-3317.