Coagulation factors VII, IX and X are effective antibacterial proteins against drug-resistant Gram-negative bacteria.
Cell Res
; 29(9): 711-724, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31399697
ABSTRACT
Infections caused by drug-resistant "superbugs" pose an urgent public health threat due to the lack of effective drugs; however, certain mammalian proteins with intrinsic antibacterial activity might be underappreciated. Here, we reveal an antibacterial property against Gram-negative bacteria for factors VII, IX and X, three proteins with well-established roles in initiation of the coagulation cascade. These factors exert antibacterial function via their light chains (LCs). Unlike many antibacterial agents that target cell metabolism or the cytoplasmic membrane, the LCs act by hydrolyzing the major components of bacterial outer membrane, lipopolysaccharides, which are crucial for the survival of Gram-negative bacteria. The LC of factor VII exhibits in vitro efficacy towards all Gram-negative bacteria tested, including extensively drug-resistant (XDR) pathogens, at nanomolar concentrations. It is also highly effective in combating XDR Pseudomonas aeruginosa and Acinetobacter baumannii infections in vivo. Through decoding a unique mechanism whereby factors VII, IX and X behave as antimicrobial proteins, this study advances our understanding of the coagulation system in host defense, and suggests that these factors may participate in the pathogenesis of coagulation disorder-related diseases such as sepsis via their dual functions in blood coagulation and resistance to infection. Furthermore, this study may offer new strategies for combating Gram-negative "superbugs".
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator IX
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Fator VII
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Fator X
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Farmacorresistência Bacteriana
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Bactérias Gram-Negativas
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China