Brenz Yannick, Ohnezeit Denise, Winther-Larsen Hanne C, Hagedorn Monica
Department of Parasitology, Bernhard Nocht Institute for Tropical MedicineHamburg, Germany.
Institute for Medical Microbiology, Hygiene and Virology, University Medical Center Hamburg-EppendorfHamburg, Germany.
Front Cell Infect Microbiol. 2017 Jun 21;7:282. doi: 10.3389/fcimb.2017.00282. eCollection 2017.
The genus comprises highly pathogenic bacteria that can cause fatal disease in their vertebrate and invertebrate hosts including humans. In general, growth depends on iron availability, hence, iron homeostasis must be tightly regulated during infection. We used the system of the professional phagocyte and the fish pathogen subsp. (.) to investigate the role of the host cell iron transporters Nramp (natural resistance associated macrophage proteins) during infection. Like its mammalian ortholog, Nramp1 transports iron from the phagosome into the cytosol, whereas the paralog NrampB is located on the contractile vacuole and controls, together with Nramp1, the cellular iron homeostasis. In , Nramp1 localized to the .-phagosome but disappeared from the compartment dependent on the presence of IglC, an established virulence factor. In the absence of Nramp transporters the bacteria translocated more efficiently from the phagosome into the host cell cytosol, its replicative niche. Increased escape rates coincided with increased proteolytic activity in bead-containing phagosomes indicating a role of the Nramp transporters for phagosomal maturation. In the mutants, a higher bacterial load was observed in the replicative phase compared to wild-type host cells. Upon bacterial access to the cytosol of wt cells, mRNA levels of bacterial iron uptake factors were transiently upregulated. Decreased iron levels in the mutants were compensated by a prolonged upregulation of the iron scavenging system. These results show that Nramps contribute to host cell immunity against infection by influencing the translocation efficiency from the phagosome to the cytosol but not by restricting access to nutritional iron in the cytosol.
该属包含高致病性细菌，可在包括人类在内的脊椎动物和无脊椎动物宿主中引发致命疾病。一般来说，细菌生长依赖铁的可利用性，因此在感染过程中必须严格调控铁稳态。我们利用专业吞噬细胞和鱼类病原体亚种（.）的系统来研究宿主细胞铁转运蛋白Nramp（天然抗性相关巨噬细胞蛋白）在感染过程中的作用。与它的哺乳动物同源物一样，Nramp1将铁从吞噬体转运到细胞质中，而旁系同源物NrampB位于收缩泡上，并与Nramp1一起控制细胞内铁稳态。在（此处原文可能有缺失信息）中，Nramp1定位于（此处原文可能有缺失信息）吞噬体，但会根据既定毒力因子IglC的存在从该隔室消失。在没有Nramp转运蛋白的情况下，细菌从吞噬体更有效地转运到宿主细胞细胞质（其复制位点）中。逃逸率增加与含珠吞噬体中蛋白水解活性增加相一致，表明Nramp转运蛋白在吞噬体成熟中发挥作用。在（此处原文可能有缺失信息）突变体中，与野生型宿主细胞相比，在复制阶段观察到更高的细菌载量。当细菌进入野生型细胞的细胞质时，细菌铁摄取因子的mRNA水平会短暂上调。（此处原文可能有缺失信息）突变体中铁水平的降低通过铁清除系统的延长上调得到补偿。这些结果表明，Nramp通过影响从吞噬体到细胞质的转运效率，而不是通过限制对细胞质中营养铁的获取，来促进宿主细胞对（此处原文可能有缺失信息）感染的免疫。
