Strain-Specific Interactions of Listeria monocytogenes with the Autophagy System in Host Cells.
Strain-Specific Interactions of Listeria monocytogenes with the Autophagy System in Host Cells.
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李斯特菌单核细胞增生李斯特菌与宿主细胞中自噬系统的菌株特异性相互作用。
DOI：
10.1371/journal.pone.0125856
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Brumell JH
中科院分区：
文献类型：
--
作者：
Cemma M;Lam GY;Stöckli M;Higgins DE;Brumell JH
单核细胞增多性李斯特菌是一种能在宿主细胞胞浆中复制的胞内致病菌。这些细菌通过ActA的表达在细胞质中进行基于肌动蛋白的运动，ActA将宿主肌动蛋白调节蛋白招募到细菌表面。单核细胞增多性乳杆菌被认为通过使用Acta依赖机制的自噬来逃避杀戮。自噬逃避的非Acta机制也已被提出，但仍知之甚少。在这里，我们检测了单核细胞增多性李斯特菌菌株10403S和eGD-e的非运动性(ΔActa)突变体的自噬作用，这两个菌株是这种病原体的两个常用研究菌株。ΔActA突变体在其表面积累泛素化蛋白和p62/SQSTM1.然而，只有eGd-eΔActa株在感染后8h显示与自噬标志物Lc3共定位。10403SΔActA需要一种抑菌剂(氯霉素)，这表明这些细菌产生了一个自噬逃避因子。内毒素K被认为可以阻断宿主细胞胞浆中单核细胞增多性李斯特菌的自噬。然而，在菌株10403S的野生型或ΔActA背景中，in1K的缺失对细菌的自噬逃避没有影响，表明它在逃避自噬中不起重要作用。EGd-e株和10403S株的ΔActa突变体在巨噬细胞中的复制与其亲本野生型株相似。因此，单核细胞增多性李斯特氏菌的ΔActa突变体可以在蛋白质泛素化的下游阻止自噬杀死细菌，对于菌株eGd-e，可以阻止自噬进入细菌的下游。我们的发现突显了单核细胞增多性李斯特氏菌在宿主细胞中通过自噬逃避杀戮机制的菌株特异性差异。
Listeria monocytogenes is an intracellular bacterial pathogen that can replicate in the cytosol of host cells. These bacteria undergo actin-based motility in the cytosol via expression of ActA, which recruits host actin-regulatory proteins to the bacterial surface. L. monocytogenes is thought to evade killing by autophagy using ActA-dependent mechanisms. ActA-independent mechanisms of autophagy evasion have also been proposed, but remain poorly understood. Here we examined autophagy of non-motile (ΔactA) mutants of L. monocytogenes strains 10403S and EGD-e, two commonly studied strains of this pathogen. The ΔactA mutants displayed accumulation of ubiquitinated proteins and p62/SQSTM1 on their surface. However, only strain EGD-e ΔactA displayed colocalization with the autophagy marker LC3 at 8 hours post infection. A bacteriostatic agent (chloramphenicol) was required for LC3 recruitment to 10403S ΔactA, suggesting that these bacteria produce a factor for autophagy evasion. Internalin K was proposed to block autophagy of L. monocytogenes in the cytosol of host cells. However, deletion of inlK in either the wild-type or ΔactA background of strain 10403S had no impact on autophagy evasion by bacteria, indicating it does not play an essential role in evading autophagy. Replication of ΔactA mutants of strain EGD-e and 10403S was comparable to their parent wild-type strain in macrophages. Thus, ΔactA mutants of L. monocytogenes can block killing by autophagy at a step downstream of protein ubiquitination and, in the case of strain EGD-e, downstream of LC3 recruitment to bacteria. Our findings highlight the strain-specific differences in the mechanisms that L. monocytogenes uses to evade killing by autophagy in host cells.
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影响因子：
3.7
作者：
Bruno JC Jr;Freitag NE
通讯作者：
Freitag NE
影响因子：
6.7
作者：
Ragon, Marie;Wirth, Thierry;Hollandt, Florian;Lavenir, Rachel;Lecuit, Marc;Le Monnier, Alban;Brisse, Sylvain
通讯作者：
Brisse, Sylvain
ACTA中的三个区域促进了ARP2/3复合介导的肌动蛋白成核和单核细胞增生李斯特菌的运动。
影响因子：
7.8
作者：
Skoble, J;Portnoy, D A;Welch, M D
通讯作者：
Welch, M D
影响因子：
6.7
作者：
Dortet L;Mostowy S;Samba-Louaka A;Gouin E;Nahori MA;Wiemer EA;Dussurget O;Cossart P
通讯作者：
Cossart P
影响因子：
4.8
作者：
Mostowy, Serge;Sancho-Shimizu, Vanessa;Cossart, Pascale
通讯作者：
Cossart, Pascale