Abstract
Ixodes scapularis ticks transmit several pathogens to humans including rickettsial bacterium, Anaplasma phagocytophilum. Here, we report that A. phagocytophilum uses tick transcriptional activator protein-1 (AP-1) as a molecular switch in the regulation of arthropod antifreeze gene, iafgp. RNAi-mediated silencing of ap-1 expression significantly affected iafgp gene expression and A. phagocytophilum burden in ticks upon acquisition from the murine host. Gel shift assays provide evidence that both the bacterium and AP-1 influences iafgp promoter and expression. The luciferase assays revealed that a region of approximately 700 bp upstream of the antifreeze gene is sufficient for AP-1 binding to promote iafgp gene expression. Furthermore, survival assays revealed that AP-1-deficient ticks were more susceptible to cold in comparison to the mock controls. In addition, this study also indicates arthropod AP-1 as a global regulator for some of the tick genes critical for A. phagocytophilum survival in the vector. In summary, our study defines a novel mode of arthropod signaling for the survival of both rickettsial pathogen and its medically important vector in the cold.
Highlights
Human anaplasmosis is one of the most common arthropod-borne diseases in the United States
We reported the identification of a novel antifreeze molecule from ticks[12] and designated it as IAFGP (I. scapularis antifreeze glycoprotein)
We reported that A. phagocytophilum modulates expression of organic anion transporting polypeptide (OATP) and kynurenine aminotransferase (KAT) pathway for its survival in ticks[16]
Summary
Human anaplasmosis is one of the most common arthropod-borne diseases in the United States. The arthropod molecular signaling that A. phagocytophilum modulates to survive in its vector host during overwintering stages is not understood. RNAi studies showed the importance of IAFGP for the survival of I. scapularis ticks in a cold environment[12]. Studies in delineating molecular gene regulation of this important tick gene (iafgp) upon A. phagocytophilum infection and survival in ticks during cold are not yet described. AP-1 family comprises of homo- and hetero-dimer members of protein families that include Jun (c-Jun, JunB and JunD), Fos (c-Fos, FosB, Fra-1 and Fra-2), ATF (ATF2, ATF3/LRF1, B-ATF, JDP1 and JDP2) and MAF (c-Maf, MafB, MafA, MafG/K and Nrl)[25,26,27,28,29]. We show that A. phagocytophilum uses arthropod AP-1 molecule as a molecular switch to regulate tick antifreeze gene that is important for both vector and pathogen survival in the cold
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