Export of a Vibrio parahaemolyticus toxin by the Sec and type III secretion machineries in tandem
Export of a Vibrio parahaemolyticus toxin by the Sec and type III secretion machineries in tandem
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DOI：
10.1038/s41564-019-0368-y
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发表时间：
2019-05-01
影响因子：
28.3
通讯作者：
Kodama, Toshio
中科院分区：
文献类型：
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作者：
Matsuda, Shigeaki;Okada, Ryu;Kodama, Toshio
许多革兰氏阴性病原体利用专门的分泌系统输出毒力因子，如外毒素和效应物(1-4)。几种外毒素被合成为含有氨基末端SEC信号肽的前体，并通过内膜结合的SEC机制输出到周质，然后使用II型分泌系统(T2SS)(3，5)跨外膜分泌到外部。在这里，我们报道了耐热的直接溶血素(TdH)，一种食源性副溶血性弧菌的外毒素，可以通过III型分泌系统(T3SS)输出，T3SS参与效应分子(4)的一步分泌，尽管具有SEC信号肽，主要通过T2SS分泌。尽管TdH的前体是针对SEC途径的，但观察到一小部分成熟的TdH重新进入细菌细胞质。成熟TdH的N端包括T3SS信号序列，使其能够加载到T3SS中。我们还表明，T3SS递送的TdH作为效应器，在副溶血性弧菌感染的兔腹泻模型中有助于肠液积累。因此，我们的结果表明，细菌毒素通过T3SS和SEC机制的非常规输出机制促进了副溶血性弧菌的毒力特征。
Many Gram-negative pathogens utilize dedicated secretion systems to export virulence factors such as exotoxins and effectors(1-4). Several exotoxins are synthesized as precursors containing amino-terminal Sec signal peptides and are exported through the inner-membrane-bound Sec machinery to the periplasm, followed by secretion across the outer membrane to the exterior using a type II secretion system (T2SS)(3,5). Here, we report that thermostable direct haemolysin (TDH), an exotoxin of the food-borne pathogen Vibrio parahaemolyticus, can be exported through the type III secretion system (T3SS), which engages in one-step secretion of effectors(4), despite possessing a Sec signal peptide and being mainly secreted via the T2SS. Although the precursor of TDH is targeted to the Sec pathway, a fraction of mature TDH was observed to re-enter the bacterial cytoplasm. The N terminus of mature TDH comprises a T3SS signal sequence, allowing it to be loaded into the T3SS. We also show that T3SS-delivered TDH as an effector contributes to intestinal fluid accumulation in a rabbit diarrhoeal model of V. parahaemolyticus infection. Thus, our results show that an unconventional export mechanism for a bacterial toxin via the T3SS in tandem with the Sec machinery facilitates the virulence trait of V. parahaemolyticus.