The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi.
The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi.
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DOI：
10.1128/jb.00647-16
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发表时间：
2017-02-15
影响因子：
3.2
通讯作者：
Frankel G
中科院分区：
文献类型：
--
作者：
Johnson R;Byrne A;Berger CN;Klemm E;Crepin VF;Dougan G;Frankel G
各种肠道沙门氏菌血清型的菌株引起人类胃肠炎或伤寒，其毒力取决于两种III型分泌系统（沙门氏菌致病岛1 [SPI-1]和SPI-2）的作用。SptP是沙门氏菌SPI-1效应子，参与介导感染后宿主细胞骨架的恢复。SptP需要伴侣SicP来稳定和分泌。SptP与S.鼠伤寒沙门氏菌和沙门氏菌。伤寒沙门氏菌的蛋白质序列的直接比较显示，S。伤寒杆菌SptP在其分子伴侣结合结构域内具有许多氨基酸变化。随后比较ΔsptP S。伤寒和沙门氏菌。鼠伤寒沙门氏菌菌株证明，与S. S.伤寒不参与感染后的侵袭或细胞骨架恢复。研究所观察到的S.伤寒影响了其功能，揭示了伤寒沙门氏菌的致病机理。伤寒沙门氏菌SptP不能与S.鼠伤寒沙门氏菌ΔsptP由于缺乏分泌。我们进一步证明了，当S.鼠伤寒沙门氏菌SptP在S.伤寒沙门氏菌S.伤寒沙门氏菌SptP是不稳定的，尽管在用沙门氏菌的伴侣结合结构域替换伴侣结合结构域后可以恢复稳定性。鼠伤寒通过细菌双杂交分析直接评估两种血清型的SptP和SicP之间的相互作用强度，表明S。伤寒沙门氏菌SptP与SicP的相互作用明显弱于沙门氏菌中的等价蛋白。鼠伤寒综上所述，我们的研究结果表明，在S。伤寒杆菌阻碍其分子伴侣的结合，导致不稳定，阻止易位，因此限制了这种效应物的细胞内活性。 研究沙门氏菌致病机理的研究通常依赖于鼠伤寒沙门氏菌，即使伤寒沙门氏菌在人类中引起更严重的疾病。因此，理解S。伤寒的发病机制缺乏。在伤寒和非伤寒血清型之间的III型分泌系统效应子SptP的差异使我们在S.伤寒我们的研究结果表明，即使sptP的缺失导致S.鼠伤寒虽然SptP只是一个效应子，但我们的研究结果表明，这些血清型的行为是显着不同的，并确定了对S.鼠伤寒沙门氏菌的毒力可能不会转化为沙门氏菌。伤寒
Strains of the various Salmonella enterica serovars cause gastroenteritis or typhoid fever in humans, with virulence depending on the action of two type III secretion systems (Salmonella pathogenicity island 1 [SPI-1] and SPI-2). SptP is a Salmonella SPI-1 effector, involved in mediating recovery of the host cytoskeleton postinfection. SptP requires a chaperone, SicP, for stability and secretion. SptP has 94% identity between S. enterica serovar Typhimurium and S. Typhi; direct comparison of the protein sequences revealed that S. Typhi SptP has numerous amino acid changes within its chaperone-binding domain. Subsequent comparison of ΔsptP S. Typhi and S. Typhimurium strains demonstrated that, unlike SptP in S. Typhimurium, SptP in S. Typhi was not involved in invasion or cytoskeletal recovery postinfection. Investigation of whether the observed amino acid changes within SptP of S. Typhi affected its function revealed that S. Typhi SptP was unable to complement S. Typhimurium ΔsptP due to an absence of secretion. We further demonstrated that while S. Typhimurium SptP is stable intracellularly within S. Typhi, S. Typhi SptP is unstable, although stability could be recovered following replacement of the chaperone-binding domain with that of S. Typhimurium. Direct assessment of the strength of the interaction between SptP and SicP of both serovars via bacterial two-hybrid analysis demonstrated that S. Typhi SptP has a significantly weaker interaction with SicP than the equivalent proteins in S. Typhimurium. Taken together, our results suggest that changes within the chaperone-binding domain of SptP in S. Typhi hinder binding to its chaperone, resulting in instability, preventing translocation, and therefore restricting the intracellular activity of this effector. IMPORTANCE Studies investigating Salmonella pathogenesis typically rely on Salmonella Typhimurium, even though Salmonella Typhi causes the more severe disease in humans. As such, an understanding of S. Typhi pathogenesis is lacking. Differences within the type III secretion system effector SptP between typhoidal and nontyphoidal serovars led us to characterize this effector within S. Typhi. Our results suggest that SptP is not translocated from typhoidal serovars, even though the loss of sptP results in virulence defects in S. Typhimurium. Although SptP is just one effector, our results exemplify that the behavior of these serovars is significantly different and genes identified to be important for S. Typhimurium virulence may not translate to S. Typhi.