In Vitro Potential of Equine DEFA1 and eCATH1 as Alternative Antimicrobial Drugs in Rhodococcosis Treatment

In Vitro Potential of Equine DEFA1 and eCATH1 as Alternative Antimicrobial Drugs in Rhodococcosis Treatment
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DOI:
10.1128/aac.05797-11
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发表时间:
2012-04-01
影响因子:
4.9
通讯作者:
Cauchard, Julien
Cauchard, Julien
中科院分区:
医学2区
文献类型:
--
作者:
Schlusselhuber, Margot;Jung, Sascha;Cauchard, Julien

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马红球菌,红球菌病的病原体,是一种严重的病原体马驹,但也免疫缺陷的人,造成支气管肺炎。该病原体通常与肺炎克雷伯氏菌或动物链球菌一起在马驹中发现。令人担忧的是,一些R。马属菌株已经对常用的抗生素具有抗性。在本研究中,我们评估了两种马抗菌肽(AMP),eCATH 1和DEFA 1,作为新的药物在体外的潜力,对R。马及其相关病原体。结果表明,这些肽段对红球藻的生长有抑制作用,并导致红球藻死亡。equi和S.在低微摩尔浓度下对小鼠动眼动物的影响。此外,eCATH 1还能抑制K.肺炎。这两种肽都能迅速破坏R. equi膜,导致细胞裂解。有趣的是,eCATH 1与利福平具有协同作用。此外,eCATH 1在溶菌浓度下对哺乳动物细胞没有细胞毒性,即使在生理盐浓度下也保持其高杀伤活性。我们的数据表明,马AMP,特别是eCATH 1,可能是控制R的替代药物的有希望的候选者。马在单一和合并感染。
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.