Repression of tick microRNA-133 induces organic anion transporting polypeptide expression critical forAnaplasma phagocytophilumsurvival in the vector and transmission to the vertebrate host
Repression of tick microRNA-133 induces organic anion transporting polypeptide expression critical forAnaplasma phagocytophilumsurvival in the vector and transmission to the vertebrate host
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DOI：
10.1371/journal.pgen.1008856
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发表时间：
2020-07-01
期刊：
影响因子：
4.5
通讯作者：
Neelakanta, Girish
中科院分区：
文献类型：
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作者：
Ramasamy, Ellango;Taank, Vikas;Neelakanta, Girish
MicroRNAs(MiRNAs)是基因表达的重要调节因子。在这项研究中，我们首次提供证据表明，立克次体病原体吞噬细胞性无浆体感染导致扁虱microRNA-133(miR-133)下调，诱导肩部硬蜱有机阴离子运输多肽(Isatp4056)基因表达，该基因对这种细菌在载体中的生存和向脊椎动物宿主的传播至关重要。用含有转录融合基因的重组载体进行的转染研究证实了miR-133与isatp4056mRNA的结合。用miR-133抑制剂处理后，扁虱和扁虱细胞的细菌载量和atp4056的表达增加。相反，用miR-133模拟或前mir-133处理后，扁虱和扁虱细胞中的p4056等位基因表达和细菌载量显著减少。此外，用Pre-mir-133感染载体处理硬蜱，可引起小鼠宿主的吞噬细胞感染。这些结果为了解硬壳病miRNAs的调控对病原体在载体中的定植及其传播感染脊椎动物宿主的影响提供了新的见解。作者摘要本研究提供了新的证据，表明节肢动物microRNA-133下调导致有机阴离子转运多肽的表达增强不仅对立克次体病原体在硬体中的存活至关重要，而且对细菌从载体传递到脊椎动物宿主也是至关重要的。了解病原体如何为了它们的利益而操纵媒介信号转导系统，将导致开发策略来阻止它们从媒介传播到脊椎动物宿主。
The microRNAs (miRNAs) are important regulators of gene expression. In this study, we provide evidence for the first time to show that rickettsial pathogenAnaplasma phagocytophiluminfection results in the down-regulation of tick microRNA-133 (miR-133), to induceIxodes scapularisorganic anion transporting polypeptide (isoatp4056) gene expression critical for this bacterial survival in the vector and for its transmission to the vertebrate host. Transfection studies with recombinant constructs containing transcriptional fusions confirmed binding of miR-133 toisoatp4056mRNA. Treatment with miR-133 inhibitor resulted in increased bacterial burden andisoatp4056expression in ticks and tick cells. In contrast, treatment with miR-133 mimic or pre-mir-133 resulted in dramatic reduction inisoatp4056expression and bacterial burden in ticks and tick cells. Moreover, treatment of ticks with pre-mir-133 affected vector-mediatedA.phagocytophiluminfection of murine host. These results provide novel insights to understand impact of modulation of tick miRNAs on pathogen colonization in the vector and their transmission to infect the vertebrate host.Author summary This study provides novel evidence that shows that down-regulation of arthropod microRNA-133 leading to enhanced expression of organic anion transporting polypeptide is not only critical for rickettsial pathogenAnaplasma phagocytophilumsurvival in ticks but also for this bacterial transmission from vector to the vertebrate host. Understanding how pathogens manipulate vector-signaling repertoire for their benefit would lead to the development of strategies to block their transmission from vector to the vertebrate host.