Actively persistent Salmonella A proportion of Salmonella cells can enter a reversible state of growth arrest, which allows them to tolerate environmental stress such as antibiotics. Stapels et al. found that these cells are not dormant but are actively modulating their environment. Salmonella within their host macrophage niche deployed a specialized type 3 secretory system called SPI-2 to deliver virulence factors, including SteE, into host cells. SteE changed the cytokine profile of the infected macrophages to reprogram them into a noninflammatory and infection-permissive state. Thus, when antibiotics were removed, the Salmonella could reemerge and cause disease. Science, this issue p. 1156 Antibiotic-tolerant, nongrowing Salmonella persister cells modulate the host cell environment to ensure regrowth upon antibiotic removal. Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing Salmonella cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.

中文翻译：

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沙门氏菌持久性在抗生素治疗期间破坏宿主免疫防御

积极持久的沙门氏菌 一部分沙门氏菌细胞可以进入可逆的生长停滞状态，这使它们能够耐受抗生素等环境压力。斯塔佩斯等人。发现这些细胞不是处于休眠状态，而是在积极地调节它们的环境。宿主巨噬细胞生态位内的沙门氏菌部署了一种称为 SPI-2 的特殊 3 型分泌系统，以将毒力因子（包括 SteE）传递到宿主细胞中。SteE 改变了受感染巨噬细胞的细胞因子谱，将它们重新编程为非炎症和感染允许状态。因此，当抗生素被去除时，沙门氏菌可能会重新出现并引起疾病。科学，这个问题 p。1156 耐抗生素、不生长的沙门氏菌持久性细胞调节宿主细胞环境，以确保去除抗生素后重新生长。许多细菌感染难以治疗并且容易复发，这可能是由于存在耐抗生素的持续存在。在体外，持久细胞似乎处于休眠状态。巨噬细胞摄取沙门氏菌后，也会出现不生长的持久性细菌，但对它们的生理状态知之甚少。在这项工作中，我们表明在巨噬细胞感染期间产生的沙门氏菌持久性保持代谢活跃状态。持久性通过沙门氏菌致病岛 2 型 3 分泌系统分泌的效应物重新编程巨噬细胞。这些效应物抑制了促炎先天免疫反应并诱导了抗炎巨噬细胞极化。这种重编程使未生长的沙门氏菌细胞在宿主中存活更长的时间。