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

	Efficacy of OH-CATH30 and Its Analogs against Drug-Resistant Bacteria In Vitro and in Mouse Models
	Li SA 1,2; Lee WH1; Zhang Y1; leewh@mail.kiz.ac.cn ; zhangy@mail.kiz.ac.cn
	2012
发表期刊	ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷号	56 期号:6 页码:3309-3317
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.
资助者	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). ; 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). ; 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). ; 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).
收录类别	SCI
语种	英语
资助者	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). ; 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). ; 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). ; 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).
WOS记录号	WOS:000304432800068
引用统计
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/7061
专题	科研部门_生物毒素与人类疾病（张云）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	leewh@mail.kiz.ac.cn; zhangy@mail.kiz.ac.cn
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,et al. 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,leewh@mail.kiz.ac.cn,&zhangy@mail.kiz.ac.cn.(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.

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