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马 DEFAl 和 eCATHl 在治疗红斑丹毒丝菌病中的体外抗菌潜力。

In vitro potential of equine DEFA1 and eCATH1 as alternative antimicrobial drugs in rhodococcosis treatment.

机构信息

Bacteriology and Parasitology Unit, Dozulé Laboratory for Equine Diseases, ANSES, Goustranville, Dozulé, France.

出版信息

Antimicrob Agents Chemother. 2012 Apr;56(4):1749-55. doi: 10.1128/AAC.05797-11. Epub 2012 Jan 9.

Abstract

Rhodococcus equi, the causal agent of rhodococcosis, is a severe pathogen of foals but also of immunodeficient humans, causing bronchopneumonia. The pathogen is often found together with Klebsiella pneumoniae or Streptococcus zooepidemicus in foals. Of great concern is the fact that some R. equi strains are already resistant to commonly used antibiotics. In the present study, we evaluated the in vitro potential of two equine antimicrobial peptides (AMPs), eCATH1 and DEFA1, as new drugs against R. equi and its associated pathogens. The peptides led to growth inhibition and death of R. equi and S. zooepidemicus at low micromolar concentrations. Moreover, eCATH1 was able to inhibit growth of K. pneumoniae. Both peptides caused rapid disruption of the R. equi membrane, leading to cell lysis. Interestingly, eCATH1 had a synergic effect together with rifampin. Furthermore, eCATH1 was not cytotoxic against mammalian cells at bacteriolytic concentrations and maintained its high killing activity even at physiological salt concentrations. Our data suggest that equine AMPs, especially eCATH1, may be promising candidates for alternative drugs to control R. equi in mono- and coinfections.

摘要

马红球菌是马传染性胸膜肺炎的病原体,也是免疫功能低下人群的严重致病菌,可引起支气管肺炎。该病原体常与肺炎克雷伯菌或兽疫链球菌一起存在于幼驹中。令人担忧的是,一些马红球菌菌株已经对常用抗生素产生了耐药性。在本研究中,我们评估了两种马属抗菌肽(AMPs),eCATH1 和 DEFA1,作为治疗马红球菌及其相关病原体的新药的体外潜力。这些肽在低微摩尔浓度下即可抑制马红球菌和兽疫链球菌的生长并导致其死亡。此外,eCATH1 能够抑制肺炎克雷伯菌的生长。两种肽均能迅速破坏马红球菌的膜,导致细胞裂解。有趣的是,eCATH1 与利福平具有协同作用。此外,在杀菌浓度下,eCATH1 对哺乳动物细胞没有细胞毒性,并且即使在生理盐浓度下,其仍保持高杀伤活性。我们的数据表明,马属抗菌肽,特别是 eCATH1,可能是控制单重和混合感染马红球菌的替代药物的有前途的候选药物。

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