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首页> 外文期刊>Journal of Medical Microbiology: An Official Journal of the Pathological Society of Great Britain and Ireland >Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei
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Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei

机译：新颖的工程阳离子抗菌肽对Francisella Tularentsis，Yersinia Pestis和Burkholderia Pseudomallei的广谱活动显示广谱活动

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摘要

Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL-37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50?% killing of F. tularensis at a concentration of 12.5?μM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections.
机译：在确认病原体的身份之前，需要在发生大流行或故意释放病原体的情况下有效治疗感染的患者。工程化阳离子抗微生物肽（ECAPS）对许多细菌病原体的显示活动，包括多种耐药菌株。将两种铅Ecaps，WLBU2和WR12与人类疗法（LL-37）进行比较，针对三种高度致病的细菌：Francisella Tularensis，Yersinia Pestis和Burkholderia pseudomallei。 WLBU2和WR12均显示出大于LL-37的杀菌活性，特别是针对F. Tultensis和Y.Pestis。只有WLBU2对B.Pseudomallei的杀菌活性才有杀菌活性。 WLBU2，WR12和LL-37都能够在体外抑制三种细菌的生长。因为这些细菌可以是兼性细胞内病原体，优先感染巨噬细胞和树突细胞，我们在用J774细胞中评估了在EX体内感染模型中的WLBU2对F.Tularensis的活性，小鼠巨噬细胞系。在该模型中，WLBU2能够以12.5Ωμm的浓度达到大于50μm的杀灭F. tultensis。这些数据显示ECAPS，特别是WLBU2的治疗潜力，作为用于治疗高致病性细菌感染的广谱抗微生物剂。

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