Journal
CELL RESEARCH
Volume 29, Issue 9, Pages 711-724Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41422-019-0202-3
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Funding
- National Key Research and Development Project [2017YFA0504300]
- National Natural Science Foundation of China [81490752, 31671347, 31771441, 21602147, 31371325]
- Doctoral Programs Foundation of the Ministry of Education of China [20130181130010]
- Research Foundation of Sichuan University for Excellent Youth Scholars [2015SCU04A23]
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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.
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