Pathogenic bacteria can alter host gene expression through post-translational modifications of histones. We show that a natural colonizer, Streptococcus pneumoniae, induces specific histone modifications, including robust dephosphorylation of histone H3 on serine 10 (H3S10), during infection of respiratory epithelial cells. The bacterial pore-forming toxin pneumolysin (PLY), along with the pyruvate oxidase SpxB responsible for H₂O₂ production, play important roles in the induction of this modification. The combined effects of PLY and H₂O₂ trigger host signaling that culminates in H3S10 dephosphorylation, which is mediated by the host cell phosphatase PP1. Strikingly, S. pneumoniae infection induces dephosphorylation and subsequent activation of PP1 catalytic activity. Colonization of PP1 catalytically deficient cells results in impaired intracellular S. pneumoniae survival and infection. Interestingly, PP1 activation and H3S10 dephosphorylation are not restricted to S. pneumoniae and appear to be general epigenomic mechanisms favoring intracellular survival of pathogenic bacteria.

病原细菌可以通过组蛋白的翻译后修饰来改变宿主基因的表达。我们显示天然定居者，肺炎链球菌，诱导呼吸道上皮细胞感染期间，特定的组蛋白修饰，包括在丝氨酸10（H3S10）上的组蛋白H3的强力去磷酸化。细菌成孔毒素肺炎球菌溶血素（PLY），以及负责产生H ₂ O ₂的丙酮酸氧化酶SpxB ，在诱导这种修饰中起重要作用。PLY和H ₂ O ₂的共同作用触发了宿主信号，该信号最终由宿主细胞磷酸酶PP1介导的H3S10去磷酸化。引人注目的是，肺炎链球菌感染会引起去磷酸化并随后激活PP1催化活性。PP1催化缺陷细胞的定殖会导致细胞内肺炎链球菌存活和感染受损。有趣的是，PP1激活和H3S10去磷酸化不仅限于肺炎链球菌，而且似乎是有利于病原菌细胞内存活的一般表观基因组机制。