Rickettsial Pathogen Perturbs Tick Circadian Gene to Infect the Vertebrate Host

Abstract

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h light: 12 h dark conditions. Moreover, A. phagocytophilum significantly modulates the oscillation pattern of expression of these genes. In addition, increased levels of clock and bmal1 and decreased expression of Toll and JAK/STAT pathway immune genes such as pelle and jak, respectively, were noted during A. phagocytophilum transmission from ticks to the vertebrate host. RNAi-mediated knockdown of clock gene expression in ticks resulted in the reduced expression of jak and pelle that increased bacterial transmission from ticks to the murine host. Furthermore, clock-deficient ticks fed late and had less engorgement weights. These results indicate an important role for circadian modulation of tick gene expression that is critical for arthropod blood feeding and transmission of pathogens from vector to the vertebrate host.

Rickettsial pathogen inhibits tick cell death through tryptophan metabolite mediated activation of p38 MAP kinase

“…phagocytophilum also modulates various signaling cascades to survive in ticks. 1 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 …”

Anti-tick vaccine candidate subolesin is important for blood feeding and innate immune gene expression in soft ticks

“…Orthologs of Toll, cystatin, fibrinogen domain-containing protein (FDP), Lysozyme precursor (Lp) and ML-domain proteins (MLD) have been identified in several ticks [ 14 , 29 – 35 ]. To identify whether O .…”

“…RNAi interference is a widely used technique in addressing the role of tick genes in blood feeding and pathogen interactions [ 16 , 17 , 20 , 35 , 41 – 50 ]. Our study provided evidence for the use of an in vitro feeding system to knockdown gene expression in O .…”

“…Orthologs of Toll, cystatin, fibrinogen domain-containing protein (FDP), Lysozyme precursor (Lp) and ML-domain proteins (MLD) have been identified in several ticks [14,[29][30][31][32][33][34][35]. To identify whether O. turicata americanus also encode these genes in its genome, we first screened the previously published transcriptome data [36].…”

Identification of a rickettsial endosymbiont in a soft tick Ornithodoros turicata americanus

“…QRT-PCR analysis was performed as with CFX OPUS instrument (BioRad, USA) with conditions as described in our previous studies [45][46][47]. Briefly, total DNA from individual nymphal or adult ticks or pool of eight eggs was extracted with the Qiagen DNeasy Blood & Tissue Kit (Qiagen, Valencia, USA) according to the manufacturer's instruction.…”