Rickettsial pathogen uses arthropod tryptophan pathway metabolites to evade reactive oxygen species in tick cells.
Cell Microbiol
; 22(10): e13237, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32562372
ABSTRACT
Reactive oxygen species (ROS) that are induced upon pathogen infection plays an important role in host defence. The rickettsial pathogen Anaplasma phagocytophilum, which is primarily transmitted by Ixodes scapularis ticks 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 in A. phagocytophilum infection in ticks. Our results show that A. phagocytophilum and hemin induce activation of l-tryptophan pathway in tick cells. Xanthurenic acid (XA), a tryptophan metabolite, supports A. phagocytophilum growth in tick cells through inhibition of tryptophan dioxygenase (TDO) activity leading to reduced l-kynurenine levels that subsequently affects build-up of ROS. However, hemin supports A. phagocytophilum growth in tick cells by inducing TDO activity leading to increased l-kynurenine levels and ROS production. Our data reveal that XA and kynurenic acid (KA) chelate hemin. Furthermore, treatment of tick cells with 3-hydroxyl l-kynurenine limits A. phagocytophilum growth in tick cells. RNAi-mediated knockdown of kynurenine aminotransferase expression results in increased ROS production and reduced A. phagocytophilum burden in tick cells. Collectively, these results suggest that l-tryptophan pathway metabolites influence A. phagocytophilum survival by affecting build up of ROS levels in tick cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Triptófano
/
Ixodes
/
Anaplasma phagocytophilum
Límite:
Animals
Idioma:
En
Revista:
Cell Microbiol
Asunto de la revista:
MICROBIOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos