Cryptdin-2: a novel therapeutic agent for experimental Salmonella Typhimurium infection

Cryptdin-2: a novel therapeutic agent for experimental Salmonella Typhimurium infection
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DOI:
10.1093/jac/dkq066
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发表时间:
2010-05-01
影响因子:
5.2
通讯作者:
Rishi, Praveen
Rishi, Praveen
中科院分区:
医学2区
文献类型:
--
作者:
Preet, Simran;Verma, Indu;Rishi, Praveen

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沙门氏菌感染是一个主要的健康危害,并已负责一些流行病。鉴于多重耐药沙门氏菌菌株的出现,需要治疗替代品。为探讨cryptdin-2(Paneth细胞抗菌肽)对沙门氏菌感染的治疗作用,采用体外、离体和体内试验方法,以菌落计数法测定cryptdin-2对鼠伤寒沙门氏菌NCTC 74的杀菌活性,结果表明cryptdin-2对鼠伤寒沙门氏菌的最低杀菌浓度(MBC)为19 mg/L。离体研究表明,与未处理的巨噬细胞相比,用cryptdin-2处理的巨噬细胞对细菌的细胞内杀伤显著更高。用cryptdin-2治疗感染的小鼠导致沙门氏菌从肝、脾和肠中显著清除。cryptdin-2的治疗功效表明,它可能是对抗沙门氏菌感染的有希望的选择,或者至少可以作为常规抗生素的辅助剂。
Salmonella infections represent a major health hazard and have been responsible for a number of epidemics. In view of the emergence of multidrug-resistant Salmonella strains, there is a need for therapeutic alternatives. The purpose of this study was to evaluate the therapeutic potential of cryptdin-2 (a Paneth cell antimicrobial peptide) against Salmonella infection.The bactericidal activity of cryptdin-2 against Salmonella enterica serovar Typhimurium NCTC74 was evaluated in vitro, ex vivo and in vivo on the basis of cfu enumeration.The MBC of cryptdin-2 for Salmonella Typhimurium was found to be 19 mg/L. The ex vivo study demonstrated significantly higher intracellular killing of the bacteria by macrophages treated with cryptdin-2 as compared with untreated macrophages. Treatment of infected mice with cryptdin-2 resulted in significant clearance of Salmonella from livers, spleens and intestines.The therapeutic efficacy of cryptdin-2 suggests that it may be a promising option to combat Salmonella infections or at least may act as an adjunct to conventional antibiotics.