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- Title
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.
- Authors
Ramasamy, Ellango; Taank, Vikas; Anderson, John F; Sultana, Hameeda; Neelakanta, Girish
- Abstract
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. 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 pathogen Anaplasma phagocytophilum survival 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.
- Subjects
ORGANIC anion transporters; ION transport (Biology); ANAPLASMOSIS; IXODES scapularis; TICKS; ANAPLASMA phagocytophilum
- Publication
PLoS Genetics, 2020, Vol 16, Issue 7, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1008856