The Ankyrin Repeat Protein RARP-1 Is a Periplasmic Factor That Supports Rickettsia parkeri Growth and Host Cell Invasion.
The Ankyrin Repeat Protein RARP-1 Is a Periplasmic Factor That Supports Rickettsia parkeri Growth and Host Cell Invasion.
复制标题
锚蛋白重复蛋白 RARP-1 是一种支持帕克立克次体生长和宿主细胞侵袭的周质因子。
DOI：
10.1128/jb.00182-22
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发表时间：
2022
影响因子：
3.2
通讯作者：
Lamason,RebeccaL
中科院分区：
文献类型：
--
作者：
Sanderlin,AllenG;Hanna,RuthE;Lamason,RebeccaL
立克次体。是专性细胞内细菌病原体，其已经进化出多种策略来利用其宿主细胞小生境。然而，导致这种细胞内生活方式的细菌因素知之甚少。在这里，我们表明，保守的锚蛋白重复蛋白RARP-1支持立克次体感染。具体而言，RARP-1促进宿主细胞在宿主细胞质内的有效进入和生长，但它不是细胞间扩散或逃避宿主自噬所必需的。我们进一步证明RARP-1不是由R. parkeri。相反，RARP-1驻留在周质中，我们确定了几个结合伙伴，预计在感染期间与RARP-1合作。总之，我们的数据显示RARP-1在立克次体生命周期中起着关键作用。是专性细胞内细菌病原体，对人类健康构成日益严重的威胁。然而，它们对宿主细胞小生境的严格依赖阻碍了对驱动立克次体感染的分子机制的研究。这项研究对立克次体锚蛋白重复蛋白RARP-1产生了急需的洞察力，RARP-1在整个属中是保守的，但尚未被功能化。早期的研究表明RARP-1分泌到宿主细胞质中。然而，这项工作的结果表明，R。parkeri RARP-1存在于周质中，并且对于宿主细胞的侵入和在宿主细胞质中的生长都是重要的。这些结果揭示RARP-1作为立克次体生命周期的新调节剂。
Rickettsiaspp. are obligate intracellular bacterial pathogens that have evolved a variety of strategies to exploit their host cell niche. However, the bacterial factors that contribute to this intracellular lifestyle are poorly understood. Here, we show that the conserved ankyrin repeat protein RARP-1 supports Rickettsia parkeri infection. Specifically, RARP-1 promotes efficient host cell entry and growth within the host cytoplasm, but it is not necessary for cell-to-cell spread or evasion of host autophagy. We further demonstrate that RARP-1 is not secreted into the host cytoplasm by R. parkeri. Instead, RARP-1 resides in the periplasm, and we identify several binding partners that are predicted to work in concert with RARP-1 during infection. Altogether, our data reveal that RARP-1 plays a critical role in the rickettsial life cycle.IMPORTANCERickettsiaspp. are obligate intracellular bacterial pathogens that pose a growing threat to human health. Nevertheless, their strict reliance on a host cell niche has hindered investigation of the molecular mechanisms driving rickettsial infection. This study yields much-needed insight into theRickettsiaankyrin repeat protein RARP-1, which is conserved across the genus but has not yet been functionally characterized. Earlier work had suggested that RARP-1 is secreted into the host cytoplasm. However, the results from this work demonstrate that R. parkeri RARP-1 resides in the periplasm and is important both for invasion of host cells and for growth in the host cell cytoplasm. These results reveal RARP-1 as a novel regulator of the rickettsial life cycle.