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Published on: October 11, 2022
Rickettsial Pathogen Perturbs Tick Circadian Gene to Infect the Vertebrate Host
Supreet Khanal1, Vikas Taank1, John F Anderson2
1Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.
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.
Insights
The pathogen Anaplasma phagocytophilum alters tick circadian clock genes, impacting its transmission to hosts. Disrupting these clock genes increases bacterial spread and affects tick feeding behaviors.
Area of Science:
- * Vector-borne disease research
- * Tick biology and pathogen transmission
- * Circadian rhythms in arthropods
Background:
- * Ixodes scapularis ticks transmit pathogens like Anaplasma phagocytophilum.
- * Ticks are exposed to environmental factors, including light-dark cycles.
- * Circadian pathways regulate organismal responses to environmental changes.
Purpose of the Study:
- * To investigate the role of arthropod circadian genes in Anaplasma phagocytophilum transmission.
- * To determine how A. phagocytophilum affects tick circadian gene expression.
- * To assess the impact of circadian gene modulation on tick feeding and pathogen transmission.
Main Methods:
- * Exposure of ticks and tick cells to light:dark cycles to observe circadian gene expression.
- * Quantification of arthropod clock, bmal1, period, and timeless gene expression.
- * RNA interference (RNAi) to knock down clock gene expression in ticks.
- * Monitoring of bacterial transmission to a murine host and tick engorgement.
Main Results:
- * Circadian oscillation of tick clock, bmal1, period, and timeless genes observed under light:dark conditions.
- * A. phagocytophilum significantly modulated the expression patterns of these circadian genes.
- * Knockdown of clock gene expression reduced immune gene (jak, pelle) expression, increasing bacterial transmission.
- * Clock-deficient ticks exhibited delayed feeding and reduced engorgement.
Conclusions:
- * Anaplasma phagocytophilum manipulates tick circadian clock genes for successful transmission.
- * Circadian gene expression is crucial for tick blood feeding and pathogen transmission to vertebrate hosts.
- * Targeting tick circadian pathways could offer novel strategies for disease control.
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