Type II toxin/antitoxin (TA) systems contribute to the formation of persister cells and biofilm formation for many organisms. Aggregatibacter actinomycetemcomitans thrives in the complex oral microbial community subjected to continual environmental flux. Little is known regarding the presence and function of type II TA systems in this organism or their contribution to adaptation and persistence in the biofilm. We identified 11 TA systems that are conserved across all seven serotypes of A. actinomycetemcomitans and represent the RelBE, MazEF and HipAB families of type II TA systems. The systems selectively responded to various environmental conditions that exist in the oral cavity. Two putative RelBE‐like TA systems, D11S_1194‐1195 and D11S_1718‐1719 were induced in response to low pH and deletion of D11S_1718‐1719 significantly reduced metabolic activity of stationary phase A. actinomycetemcomitans cells upon prolonged exposure to acidic conditions. The deletion mutant also exhibited reduced biofilm biomass when cultured under acidic conditions. The D11S_1194 and D11S_1718 toxin proteins inhibited in vitro translation of dihydrofolate reductase (DHFR) and degraded ribosome‐associated, but not free, MS2 virus RNA. In contrast, the corresponding antitoxins (D11S_1195 and D11S_1719), or equimolar mixtures of toxin and antitoxin, had no effect on DHFR production or RNA degradation. Together, these results suggest that D11S_1194‐1195 and D11S_1718‐1719 are RelBE‐like type II TA systems that are activated under acidic conditions and may function to cleave ribosome‐associated mRNA to inhibit translation in A. actinomycetemcomitans. In vivo, these systems may facilitate A. actinomycetemcomitans adaptation and persistence in acidic local environments in the dental biofilm.

中文翻译：

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聚集和放线杆菌中II型毒素/抗毒素系统的鉴定和功能表征。

II型毒素/抗毒素（TA）系统有助于许多生物形成持久性细胞和形成生物膜。遭受连续环境变化的复杂口腔微生物群落中，放线杆菌聚集很旺。关于II型TA系统在该生物中的存在和功能或其对生物膜的适应性和持久性的贡献知之甚少。我们确定了11种在所有7种血清型的放线放线杆菌中均保守的TA系统。并代表II型TA系统的RelBE，MazEF和HipAB系列。该系统选择性地响应口腔中存在的各种环境条件。响应于低pH值，诱导了两个假定的类似RelBE的TA系统D11S_1194-1195和D11S_1718-1719，D11S_1718-1719的缺失显着降低了固定相A的代谢活性。长时间暴露于酸性条件下会导致细胞死亡。当在酸性条件下培养时，缺失突变体还表现出减少的生物膜生物量。D11S_1194和D11S_1718毒素蛋白抑制了二氢叶酸还原酶（DHFR）的体外翻译，并降解了核糖体相关但不是游离的MS2病毒RNA。相反，相应的抗毒素（D11S_1195和D11S_1719）或毒素和抗毒素的等摩尔混合物对DHFR产生或RNA降解没有影响。总之，这些结果表明D11S_1194-1195和D11S_1718-1719是RelBE样的II型TA系统，在酸性条件下被激活，并可能发挥作用，与核糖体相关的mRNA裂解以抑制A.放线菌的翻译。在体内，这些系统可能有助于放线放线杆菌 牙齿生物膜在酸性局部环境中的适应性和持久性。