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单核细胞增生李斯特菌序列类型1的高侵袭性和细胞间传播增加与李斯特菌溶素S、内化素F和内化素J1无关。

Hyperinvasiveness and increased intercellular spread of Listeria monocytogenes sequence type 1 are independent of listeriolysin S, internalin F and internalin J1.

作者信息

Rupp Sebastian, Bärtschi Michelle, Frey Joachim, Oevermann Anna

机构信息

Division of Neurological Sciences, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern CH-3001, Switzerland.

Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern CH-3001, Switzerland.

出版信息

J Med Microbiol. 2017 Jul;66(7):1053-1062. doi: 10.1099/jmm.0.000529. Epub 2017 Jul 31.

Abstract

PURPOSE

Listeria monocytogenes is a genetically heterogeneous species, which is divided into evolutionary lineages and clonal complexes (CCs). Not all L. monocytogenes isolates are equally likely to cause disease, with CC1, and in particular sequence type (ST) 1, being the most prevalent complex in human and ruminant infections and more specifically in neurolisteriosis. While the major factors that determine neurotropism are unknown, the L. monocytogenes CC1 strains harbour listeriolysin S (lls) and particular alleles of internalin (inl) F and inlJ, which are not present in CCs commonly isolated from food and the environment. The aim of this study was to analyse the role of these factors in cellular infection.

METHODOLOGY

A ST1 field strain (JF5203) from CC1 isolated from a bovine rhombencephalitis case was used to create deletion mutants. These were tested alongside the parental strain and EGD-e (CC9), in different culture models representing L. monocytogenes targets (neurons, microglia, placenta, intestine and macrophages). The phenotype was assessed by quantification of c.f.u. from cell lysates and immunofluorescence analysis.

RESULTS

Compared to EGD-e, the ST1 strain JF5203 was hyperinvasive and exhibited increased intercellular spread. However, deletion of llsB, inlF or inlJ1, had no significant effect on infection or growth in the culture models tested.

CONCLUSION

Our results underline the importance of using relevant clinical strains when investigating L. monocytogenes virulence. We show that despite the association with CC1, llsB, inlF and inlJ1 are not involved in the hyperinvasiveness and efficient intercellular spread of ST1 in various cell types.

摘要

目的

单核细胞增生李斯特菌是一个基因异质的物种,分为进化谱系和克隆复合体(CCs)。并非所有单核细胞增生李斯特菌分离株引起疾病的可能性都相同,CC1,特别是序列型(ST)1,是人类和反刍动物感染中最普遍的复合体,在神经李斯特菌病中尤为如此。虽然决定嗜神经性的主要因素尚不清楚,但单核细胞增生李斯特菌CC1菌株携带李斯特菌溶血素S(lls)以及内化素(inl)F和inlJ的特定等位基因,而这些在通常从食物和环境中分离出的CCs中不存在。本研究的目的是分析这些因素在细胞感染中的作用。

方法

从一例牛菱形脑炎病例中分离得到的来自CC1的ST1田间菌株(JF5203)用于构建缺失突变体。这些突变体与亲本菌株和EGD-e(CC9)一起,在代表单核细胞增生李斯特菌靶标的不同培养模型(神经元、小胶质细胞、胎盘、肠道和巨噬细胞)中进行测试。通过对细胞裂解物中的菌落形成单位(c.f.u.)进行定量和免疫荧光分析来评估表型。

结果

与EGD-e相比,ST1菌株JF5203具有更强的侵袭性且细胞间传播增加。然而,缺失llsB、inlF或inlJ1对所测试的培养模型中的感染或生长没有显著影响。

结论

我们的结果强调了在研究单核细胞增生李斯特菌毒力时使用相关临床菌株的重要性。我们表明,尽管与CC1有关联,但llsB、inlF和inlJ1并不参与ST1在各种细胞类型中的高侵袭性和有效的细胞间传播。

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