mcr-1 Gene Expression Modulates the Inflammatory Response of Human Macrophages to Escherichia coli.
Infect Immun
; 88(8)2020 07 21.
Article
em En
| MEDLINE
| ID: mdl-32513853
ABSTRACT
MCR-1 is a plasmid-encoded phosphoethanolamine transferase able to modify the lipid A structure. It confers resistance to colistin and was isolated from human, animal, and environmental strains of Enterobacteriaceae, raising serious global health concerns. In this paper, we used recombinant mcr-1-expressing Escherichia coli to study the impact of MCR-1 products on E. coli-induced activation of inflammatory pathways in activated THP-1 cells, which was used as a model of human macrophages. We found that infection with recombinant mcr-1-expressing E. coli significantly modulated p38-MAPK and Jun N-terminal protein kinase (JNK) activation and pNF-κB nuclear translocation as well as the expression of genes for the relevant proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-1ß compared with mcr-1-negative strains. Caspase-1 activity and IL-1ß secretion were significantly less activated by mcr-1-positive E. coli strains than the mcr-1-negative parental strain. Similar results were obtained with clinical isolates of mcr-1-positive E. coli, suggesting that, in addition to colistin resistance, the expression of mcr-1 allows the escape of early host innate defenses and may promote bacterial survival.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação da Expressão Gênica
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NF-kappa B
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Proteínas de Escherichia coli
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MAP Quinase Quinase 4
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Proteínas Quinases p38 Ativadas por Mitógeno
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Escherichia coli
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália