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The microRNAs (miRNAs) are important regulators of gene expression. In this study, we provide evidence for the first time to show that rickettsial pathogen  Anaplasma phagocytophilum  infection results in the down-regulation of tick microRNA-133 (miR-133), to induce  Ixodes scapularis  organic 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 to  isoatp4056  mRNA. Treatment with miR-133 inhibitor resulted in increased bacterial burden and  isoatp4056  expression in ticks and tick cells. In contrast, treatment with miR-133 mimic or pre-mir-133 resulted in dramatic reduction in  isoatp4056  expression and bacterial burden in ticks and tick cells. Moreover, treatment of ticks with pre-mir-133 affected vector-mediated  A .  phagocytophilum  infection 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.

plos genetics

Repression of tick microRNA-133 induces organic anion transporting polypeptide expression critical for Anaplasma phagocytophilum survival in the vector and transmission to the vertebrate host