RESUMO
Many of the world's warm-blooded species are chronically infected with Toxoplasma gondii tissue cysts, including an estimated one-third of the global human population. The cellular processes that permit long-term persistence within the cyst are largely unknown for T. gondii and related coccidian parasites that impact human and animal health. Herein, we show that genetic ablation of TgATG9 substantially reduces canonical autophagy and compromises bradyzoite viability. Transmission electron microscopy revealed numerous structural abnormalities occurring in ∆atg9 bradyzoites. Intriguingly, abnormal mitochondrial networks were observed in TgATG9-deficient bradyzoites, some of which contained numerous different cytoplasmic components and organelles. ∆atg9 bradyzoite fitness was drastically compromised in vitro and in mice, with very few brain cysts identified in mice 5 weeks post-infection. Taken together, our data suggests that TgATG9, and by extension autophagy, is critical for cellular homeostasis in bradyzoites and is necessary for long-term persistence within the cyst of this coccidian parasite.
Assuntos
Autofagia , Encéfalo/parasitologia , Proteínas de Membrana/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Toxoplasmose Cerebral/parasitologia , Animais , Encéfalo/patologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita , Humanos , Estágios do Ciclo de Vida , Proteínas de Membrana/genética , Proteínas de Membrana/ultraestrutura , Camundongos Endogâmicos CBA , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Proteínas de Protozoários/genética , Proteínas de Protozoários/ultraestrutura , Fatores de Tempo , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasma/ultraestrutura , Toxoplasmose Cerebral/patologia , Vacúolos/genética , Vacúolos/metabolismo , Vacúolos/ultraestrutura , VirulênciaRESUMO
AlanGrant, Baee, Corofin, OrangeOswald, and Vincenzo are newly isolated phages of Mycobacterium smegmatis mc(2)155 discovered in Pittsburgh, Pennsylvania, USA. All five phages share nucleotide similarity with cluster B mycobacteriophages but span considerable diversity with Corofin and OrangeOswald in subcluster B3, AlanGrant and Vincenzo in subcluster B4, and Baee in subcluster B5.