Rickettsial pathogen uses arthropod tryptophan pathway metabolites to evade reactive oxygen species in tick cells.

Reactive oxygen species (ROS) that are induced upon pathogen infection plays an important role in host defence. The rickettsial pathogenAnaplasma phagocytophilum, which is primarily transmitted byIxodes scapularisticks in the United States, has evolved many strategies to escape ROS and survive in mammalian cells. However, little is known on the role of ROS inA. phagocytophiluminfection in ticks. Our results show thatA. phagocytophilumand hemin induce activation ofl-tryptophan pathway in tick cells. Xanthurenic acid (XA), a tryptophan metabolite, supportsA. phagocytophilumgrowth in tick cells through inhibition of tryptophan dioxygenase (TDO) activity leading to reducedl-kynurenine levels that subsequently affects build-up of ROS. However, hemin supportsA. phagocytophilumgrowth in tick cells by inducing TDO activity leading to increasedl-kynurenine levels and ROS production. Our data reveal that XA and kynurenic acid (KA) chelate hemin. Furthermore, treatment of tick cells with 3-hydroxyll-kynurenine limitsA. phagocytophilumgrowth in tick cells. RNAi-mediated knockdown of kynurenine aminotransferase expression results in increased ROS production and reducedA. phagocytophilumburden in tick cells. Collectively, these results suggest thatl-tryptophan pathway metabolites influenceA. phagocytophilumsurvival by affecting build up of ROS levels in tick cells.