In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection.
In vivo transcriptional profiling of Listeria monocytogenes and mutagenesis identify new virulence factors involved in infection.
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DOI：
10.1371/journal.ppat.1000449
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发表时间：
2009-05
期刊：
影响因子：
6.7
通讯作者：
Cabanes D
中科院分区：
文献类型：
--
作者：
Camejo A;Buchrieser C;Couvé E;Carvalho F;Reis O;Ferreira P;Sousa S;Cossart P;Cabanes D
单核细胞增生李斯特菌是一种人类细胞内病原体，能够在摄入受污染的食物后定殖宿主组织，引起严重的侵入性感染。为了更好地了解宿主-病原体相互作用的本质，我们研究了L。单核细胞增多症基因组的表达。在感染小鼠的脾脏中，与在丰富肉汤培养基中的指数生长相比，李斯特菌基因组的约20%差异表达，基本上是通过基因激活。这里提供的数据表明，在感染过程中，李斯特菌处于活跃的增殖阶段，如参与复制，细胞分裂和增殖的基因的高表达所揭示的。体内细菌生长需要增加参与细菌代谢和应激反应（特别是氧化应激）适应的基因的表达。李斯特菌与宿主的相互作用诱导细胞壁代谢和毒力因子的表面表达。在感染过程中，L.单核细胞增多症还激活宿主防御的破坏机制，包括对阳离子肽的抗性、肽聚糖修饰和胞壁酰肽的释放。我们表明，李斯特菌基因组的体内差异表达是由一个复杂的调控网络协调，PrfA-SigB相互作用的核心作用。特别是L.单核细胞增多症在体内上调两种主要毒力调节因子PrfA和VirR及其下游效应物。体内诱导基因的突变允许鉴定新的L。单核细胞增多症毒力因子，包括LPXTG表面蛋白，表明S层糖蛋白和镉外排系统在李斯特菌毒力中的作用。单核细胞增生李斯特菌是一种严重的食源性疾病的病原菌。在人类中，它引起各种表现，从无症状的肠道携带和胃肠炎到侵入性和传播性严重疾病。败血症、脑膜脑炎和孕妇胎儿感染是梅毒最严重的临床特征。毒力是一种仅在易感宿主中表现的性状，涉及细菌因子和宿主成分之间的高度协调的相互作用。本文报道了使用体内基因组表达谱作为一种强大的方法，以获得详细的了解李斯特菌的反应和发生在感染小鼠的分子串扰。我们发现，在感染过程中，L。单核细胞增多症改变其整个基因组的表达以促进毒力，破坏宿主防御并适应宿主条件。本文首先分析了L.体内单核细胞增多症基因表达显著增强了我们对细胞内病原体促进感染的方式的理解。
Listeria monocytogenes is a human intracellular pathogen able to colonize host tissues after ingestion of contaminated food, causing severe invasive infections. In order to gain a better understanding of the nature of host–pathogen interactions, we studied the L. monocytogenes genome expression during mouse infection. In the spleen of infected mice, ≈20% of the Listeria genome is differentially expressed, essentially through gene activation, as compared to exponential growth in rich broth medium. Data presented here show that, during infection, Listeria is in an active multiplication phase, as revealed by the high expression of genes involved in replication, cell division and multiplication. In vivo bacterial growth requires increased expression of genes involved in adaptation of the bacterial metabolism and stress responses, in particular to oxidative stress. Listeria interaction with its host induces cell wall metabolism and surface expression of virulence factors. During infection, L. monocytogenes also activates subversion mechanisms of host defenses, including resistance to cationic peptides, peptidoglycan modifications and release of muramyl peptides. We show that the in vivo differential expression of the Listeria genome is coordinated by a complex regulatory network, with a central role for the PrfA-SigB interplay. In particular, L. monocytogenes up regulates in vivo the two major virulence regulators, PrfA and VirR, and their downstream effectors. Mutagenesis of in vivo induced genes allowed the identification of novel L. monocytogenes virulence factors, including an LPXTG surface protein, suggesting a role for S-layer glycoproteins and for cadmium efflux system in Listeria virulence. The facultative intracellular bacterial pathogen Listeria monocytogenes is the etiological agent of a severe foodborne disease. In humans it causes a variety of manifestations ranging from asymptomatic intestinal carriage and gastroenteritis to invasive and disseminated severe diseases. Septicemia, meningoencephalitis, and infection of the foetus in pregnant women are the most serious clinical features of listeriosis. Virulence is a trait that only manifests in a susceptible host, involving a highly coordinated interaction between bacterial factors and host components. This article reports the use of in vivo genome expression profiling as a powerful approach to gain a detailed understanding of the Listeria responses and the molecular cross-talk taking place in infected mice. We showed that, during infection, L. monocytogenes shifts the expression of its entire genome to promote virulence, subverting host defenses and adapting to host conditions. This first analysis of L. monocytogenes gene expression in vivo significantly enhances our understanding of the means by which intracellular pathogens promote infection.
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影响因子：
3.1
作者：
ALEXANDER, JE;ANDREW, PW;ROBERTS, IS
通讯作者：
ROBERTS, IS
影响因子：
4.8
作者：
Archambaud, Cristel;Nahori, Marie-Anne;Dussurget, Olivier
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Dussurget, Olivier
影响因子：
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作者：
Cabanes, Didier;Lecuit, Marc;Cossart, Pascale
通讯作者：
Cossart, Pascale
影响因子：
3.1
作者：
Chatterjee, SS;Hossain, H;Hain, T
通讯作者：
Hain, T
影响因子：
11.4
作者：
Brekasis, D;Paget, MSB
通讯作者：
Paget, MSB