Science2014-06-12 5:11 PM

沙门氏菌在巨噬细胞内持续存活关键原因解读 Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters

论文摘要 

在被称作巨噬细胞的免疫细胞吞噬之后,沙门氏菌会选择2种命运之一:复制或以一种低调的不复制的状态持续存在。这些持续化的细胞可能是细菌逃避抗菌素治疗并持续存留以引起持续性或反复发作性感染的一种方式。

为了更多了解有关持续细胞(persisters)是如何发育的,Sophie Helaine及其同事用一种荧光单细胞追踪技术对实验室中的以及受到感染的小鼠身上的沙门氏菌细胞进行了追踪。他们发现,该细胞的命运是在巨噬细胞内的被称作液泡的封闭隔室中决定的。

研究人员说,这些隔室是酸性的而且营养贫乏,这些条件看来能够同时触发细菌的毒力因子及持续细胞的形成。在这些液泡中存在着各种形成的持续细胞类型,而这种多样性可能也为这些细菌提供了逃避免疫检测并活着以再次感染的一种方式。


Abstract 

Many bacterial pathogens cause persistent infections despite repeated antibiotic exposure. Bacterial persisters are antibiotic-tolerant cells, but little is known about their growth status and the signals and pathways leading to their formation in infected tissues. We used fluorescent single-cell analysis to identifySalmonella persisters during infection. These were part of a nonreplicating population formed immediately after uptake by macrophages and were induced by vacuolar acidification and nutritional deprivation, conditions that also induce Salmonella virulence gene expression. The majority of 14 toxin-antitoxin modules contributed to intracellular persister formation. Some persisters resumed intracellular growth after phagocytosis by naïve macrophages. Thus, the vacuolar environment induces phenotypic heterogeneity, leading to either bacterial replication or the formation of nonreplicating persisters that could provide a reservoir for relapsing infection.

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