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首页> 外文期刊>Journal of bacteriology >Membrane Chaperone SecDF Plays a Role in the Secretion of Listeria monocytogenes Major Virulence Factors
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Membrane Chaperone SecDF Plays a Role in the Secretion of Listeria monocytogenes Major Virulence Factors

机译：膜伴侣SecDF在李斯特菌李斯特菌主要毒力因子的分泌中发挥作用

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Listeria monocytogenes is a Gram-positive human intracellular pathogen that infects diverse mammalian cells. Upon invasion, L. monocytogenes secretes multiple virulence factors that target host cellular processes and promote infection. It has been presumed, but was not empirically established, that the Sec translocation system is the primary mediator of this secretion. Here, we validate an important role for SecDF, a component of the Sec system, in the secretion of several critical L. monocytogenes virulence factors. A ΔsecDF mutant is demonstrated to exhibit impaired membrane translocation of listeriolysin O (LLO), PlcA, PlcB, and ActA, factors that mediate L. monocytogenes phagosomal escape and spread from cell to cell. This impaired translocation was monitored by accumulation of the factors on the bacterial membrane and by reduced activity upon secretion. This defect in secretion is shown to be associated with a severe intracellular growth defect of the ΔsecDF mutant in macrophages and a less virulent phenotype in mice, despite normal growth in laboratory medium. We further show that SecDF is upregulated when the bacteria reside in macrophage phagosomes and that it is necessary for efficient phagosomal escape. Taken together, these data support the premise that SecDF plays a role as a chaperone that facilitates the translocation of L. monocytogenes virulence factors during infection.
机译：单核细胞增生李斯特菌是感染多种哺乳动物细胞的革兰氏阳性人类细胞内病原体。侵袭后，单核细胞增生李斯特菌会分泌多种毒力因子，这些因子靶向宿主细胞过程并促进感染。据推测，但没有经验证明，Sec易位系统是该分泌物的主要介体。在这里，我们验证了SecDF（Sec系统的组成部分）在分泌几个关键的单核细胞增生李斯特菌毒力因子中的重要作用。已证明Δ secDF 突变体表现出李斯特菌溶血素O（LLO），PlcA，PlcB和ActA的膜易位受损，这是介导单核细胞增生李斯特氏菌吞噬体逃逸并在细胞之间扩散的因子。通过因子在细菌膜上的积累和分泌时活性的降低来监测这种受损的易位。尽管在实验室培养基中正常生长，但这种分泌缺陷与巨噬细胞中Δ secDF 突变体的严重细胞内生长缺陷和小鼠毒性较低的表型有关。我们进一步表明，当细菌驻留在巨噬细胞吞噬体中时，SecDF被上调，这对于有效的吞噬体逃逸是必要的。综上所述，这些数据支持了SecDF作为伴侣分子在感染过程中促进单核细胞增生李斯特菌毒力因子易位的前提。

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