Hamon Mélanie Anne, Batsché Eric, Régnault Béatrice, Tham To Nam, Seveau Stéphanie, Muchardt Christian, Cossart Pascale
Unité des Interactions Bactéries-Cellules, Unité de Régulation pigénétique, and Génopole, Plate-forme 2, Institut Pasteur, F-75015 Paris, France.
Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13467-72. doi: 10.1073/pnas.0702729104. Epub 2007 Aug 3.
Upon infection, pathogens reprogram host gene expression. In eukaryotic cells, genetic reprogramming is induced by the concerted activation/repression of transcription factors and various histone modifications that control DNA accessibility in chromatin. We report here that the bacterial pathogen Listeria monocytogenes induces a dramatic dephosphorylation of histone H3 as well as a deacetylation of histone H4 during early phases of infection. This effect is mediated by the major listerial toxin listeriolysin O in a pore-forming-independent manner. Strikingly, a similar effect also is observed with other toxins of the same family, such as Clostridium perfringens perfringolysin and Streptococcus pneumoniae pneumolysin. The decreased levels of histone modifications correlate with a reduced transcriptional activity of a subset of host genes, including key immunity genes. Thus, control of epigenetic regulation emerges here as an unsuspected function shared by several bacterial toxins, highlighting a common strategy used by intracellular and extracellular pathogens to modulate the host response early during infection.
感染时，病原体可重新编程宿主基因表达。在真核细胞中，基因重编程是由转录因子的协同激活/抑制以及各种控制染色质中DNA可及性的组蛋白修饰所诱导的。我们在此报告，细菌病原体单核细胞增生李斯特菌在感染早期会诱导组蛋白H3发生显著的去磷酸化以及组蛋白H4发生去乙酰化。这种效应由主要的李斯特菌毒素李斯特菌溶血素O以不依赖于成孔作用的方式介导。令人惊讶的是，在同一毒素家族的其他毒素中也观察到了类似的效应，如产气荚膜梭菌的产气荚膜溶血素和肺炎链球菌的肺炎溶血素。组蛋白修饰水平的降低与一部分宿主基因（包括关键免疫基因）转录活性的降低相关。因此，表观遗传调控的控制在此成为几种细菌毒素共有的一种意想不到的功能，突出了细胞内和细胞外病原体在感染早期调节宿主反应所采用的共同策略。
