Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2.
FASEB J
; 33(12): 13450-13464, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31569998
ABSTRACT
Iron is a necessary nutrient for humans and nearly all bacterial species. During Salmonella infection, macrophages limit the availability of iron to intracellular pathogens in one of the central components of nutritional immunity. However, Salmonella also have mechanisms to interfere with the antimicrobial effect of host iron withdrawal and meet their own nutrient requirements by scavenging iron from the host. Here, we provide what is, to our knowledge, the first report that SpvB, a pSLT-encoded cytotoxic protein whose function is associated with the intracellular stage of salmonellosis, perturbs macrophage iron metabolism, thereby facilitating Salmonella survival and intracellular replication. In investigating the underlying mechanism, we observed that the Salmonella effector SpvB down-regulated nuclear factor erythroid-derived 2-related factor 2 (NRF2), and its C-terminal domain was necessary and sufficient for NRF2 degradation via the proteasome pathway. Decreased NRF2 expression in the nucleus resulted in a decrease in its transcriptional target ferroportin, encoding the sole macrophage iron exporter, thus ultimately decreasing iron efflux and increasing the intracellular iron content. Additionally, SpvB contributes to the pathogenesis of Salmonella including severe serum hypoferremia, increased splenic and hepatic bacterial burden, and inflammatory injury in vivo. Together, our observations uncovered a novel contribution of SpvB to Salmonella pathology via interference with host intracellular iron metabolism.-Yang, S., Deng, Q., Sun, L., Dong, K., Li, Y., Wu, S., Huang, R. Salmonella effector SpvB interferes with intracellular iron homeostasis via regulation of transcription factor NRF2.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por Salmonella
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Salmonella typhimurium
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ADP Ribose Transferases
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Anemia Ferropriva
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Fatores de Virulência
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Fator 2 Relacionado a NF-E2
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Homeostase
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Ferro
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Macrófagos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China