Abstract |
Cyclic diguanylate monophosphate ( c-di-GMP) is a well-conserved second messenger in bacteria. During infection, the innate immune system can also sense c-di-GMP; however, whether bacterial pathogens utilize c-di-GMP as a weapon to fight against host defense for survival and possible mechanisms underlying this process remain poorly understood. Siderocalin (LCN2) is a key antibacterial component of the innate immune system and sequesters bacterial siderophores to prevent acquisition of iron. Here we show that c-di-GMP can directly target the human LCN2 protein to inhibit its antibacterial activity. We demonstrate that c-di-GMP specifically binds to LCN2. In addition, c-di-GMP can compete with bacterial ferric siderophores to bind LCN2. Furthermore, c-di-GMP can significantly reduce LCN2-mediated inhibition on the in vitro growth of Escherichia coli. Thus, LCN2 acts as a c-di-GMP receptor. Our findings provide insight into the mechanism by which bacteria utilize c-di-GMP to interfere with the innate immune system for survival.
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Authors | Weihui Li, Tao Cui, Lihua Hu, Ziqing Wang, Zongqiang Li, Zheng-Guo He |
Journal | Nature communications
(Nat Commun)
Vol. 6
Pg. 8330
(Sep 22 2015)
ISSN: 2041-1723 [Electronic] England |
PMID | 26390966
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acute-Phase Proteins
- Anti-Bacterial Agents
- Carrier Proteins
- LCN2 protein, human
- Lipocalin-2
- Lipocalins
- Proto-Oncogene Proteins
- Recombinant Proteins
- bis(3',5')-cyclic diguanylic acid
- Cyclic GMP
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Topics |
- Acute-Phase Proteins
(genetics, metabolism, pharmacology)
- Anti-Bacterial Agents
(metabolism)
- Carrier Proteins
(genetics, metabolism)
- Cyclic GMP
(analogs & derivatives, metabolism)
- Databases, Factual
- Escherichia coli
(genetics, metabolism)
- Gene Expression Regulation
- Humans
- Lipocalin-2
- Lipocalins
(genetics, metabolism, pharmacology)
- Models, Chemical
- Models, Molecular
- Molecular Structure
- Mycobacterium tuberculosis
(drug effects, metabolism)
- Protein Binding
- Protein Conformation
- Proto-Oncogene Proteins
(genetics, metabolism, pharmacology)
- Recombinant Proteins
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