Auto, a surface associated autolysin of Listeria monocytogenes required for entry into eukaryotic cells and virulence

Auto, a surface associated autolysin of Listeria monocytogenes required for entry into eukaryotic cells and virulence
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DOI:
10.1111/j.1365-2958.2003.03945.x
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发表时间:
2004-03-01
影响因子:
3.6
通讯作者:
Cossart, P
Cossart, P
中科院分区:
生物学2区
文献类型:
--
作者:
Cabanes, D;Dussurget, O;Cossart, P

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单核细胞增生李斯特菌是一种机会性食源性人畜致病菌。由这种细胞内病原体表达的几种表面蛋白对感染过程至关重要。通过计算机分析,我们比较了L。单核细胞增生性李斯特菌和非致病性的无害李斯特菌,并确定了编码李斯特菌表面蛋白的基因。单核细胞增多症在L.无害。我们将该基因命名为aut,它编码一个由572个氨基酸组成的蛋白质(Auto),该蛋白质含有一个信号序列、一个N端自溶素结构域和一个C端细胞壁锚定结构域,由四个GW模块组成。我们在这里表明,aut基因的表达独立的毒力基因调节PrfA和编码的表面蛋白具有自溶活性。我们提供证据证明输入L需要Auto。将单核细胞增多症转化为培养的非吞噬性真核细胞。aut缺失突变体的低侵袭性与其在小鼠静脉内接种和豚鼠口服感染后的毒力降低相关。在感染期间,Auto的自溶活性也可能是关键的。因此,Auto作为L的一种新类型出现。单核细胞增生毒力因子
Listeria monocytogenes is an opportunistic food-borne human and animal pathogen. Several surface proteins expressed by this intracellular pathogen are critical for the infectious process. By in silico analysis we compared the surface protein repertories of L. monocytogenes and of the non-pathogenic species Listeria innocua and identified a gene encoding a surface protein of L. monocytogenes absent in L. innocua. This gene that we named aut encodes a protein (Auto) of 572 amino acids containing a signal sequence, a N-terminal autolysin domain and a C-terminal cell wall-anchoring domain made up of four GW modules. We show here that the aut gene is expressed independently of the virulence gene regulator PrfA and encodes a surface protein with an autolytic activity. We provide evidence that Auto is required for entry of L. monocytogenes into cultured non-phagocytic eukaryotic cells. The low invasiveness of an aut deletion mutant correlates with its reduced virulence following intravenous inoculation of mice and oral infection of guinea pigs. During infection, the autolytic activity of Auto may also be critical. Auto appears thus as a novel type of L. monocytogenes virulence factor.