Hpt, a bacterial homolog of the microsomal glucose-6-phosphate translocase, mediates rapid intracellular proliferation in Listeria
Hpt, a bacterial homolog of the microsomal glucose-6-phosphate translocase, mediates rapid intracellular proliferation in Listeria
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DOI：
10.1073/pnas.012363899
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发表时间：
2002-01-08
影响因子：
11.1
通讯作者：
Vázquez-Boland, JA
中科院分区：
文献类型：
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作者：
Chico-Calero, I;Suárez, M;Vázquez-Boland, JA
体内的有效复制对于微寄生虫在其宿主中定殖至关重要，并且了解微生物病原体在宿主组织内生长的分子机制可以导致治疗感染的新疗法的发现。在这里，我们提出的证据表明，食源性细菌病原体单核细胞增生李斯特氏菌（一种兼性细胞内寄生虫）利用宿主细胞中的磷酸己糖（HP）作为碳和能量来源来促进细胞内快速生长。 HP 摄取由 Hpt 介导，Hpt 是哺乳动物转位酶的细菌同源物，在糖异生和糖原分解的最后步骤中，将 6-磷酸葡萄糖从细胞质转运到内质网。 Hpt 通透酶的表达受到中央毒力调节因子 PrfA 的严格控制，PrfA 进入宿主细胞后会诱导一系列李斯特菌细胞内寄生所需的毒力因子。 Hpt 的缺失导致李斯特菌胞质内增殖受损，并减弱小鼠体内的毒力。 Hpt 是第一个被鉴定为特异性参与兼性细胞内病原体复制阶段的毒力因子。这也是微生物病原体对细胞内寄生的适应如何涉及其真核宿主细胞的生理机制的模仿的一个明显例子。
Efficient replication in vivo is essential for a microparasite to colonize its host and the understanding of the molecular mechanisms by which microbial pathogens grow within host tissues can lead to the discovery of novel therapies to treat infection. Here we present evidence that the foodborne bacterial pathogen Listeria monocytogenes, a facultative intracellular parasite, exploits hexose phosphates (HP) from the host cell as a source of carbon and energy to fuel fast intracellular growth. HP uptake is mediated by Hpt, a bacterial homolog of the mammalian translocase that transports glucose-6-phosphate from the cytosol into the endoplasmic reticulum in the final step of gluconeogenesis and glycogenolysis. Expression of the Hpt permease is tightly controlled by the central virulence regulator PrfA, which upon entry into host cells induces a set of virulence factors required for listerial intracellular parasitism. Loss of Hpt resulted in impaired listerial intra-cytosolic proliferation and attenuated virulence in mice. Hpt is the first virulence factor to be identified as specifically involved in the replication phase of a facultative intracellular pathogen. It is also a clear example of how adaptation to intracellular parasitism by microbial pathogens involves mimicry of physiological mechanisms of their eukaryotic host cells.