Back to Search
Start Over
Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing.
- Source :
-
Nature communications [Nat Commun] 2019 Jul 25; Vol. 10 (1), pp. 3325. Date of Electronic Publication: 2019 Jul 25. - Publication Year :
- 2019
-
Abstract
- Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistant Escherichia coli, whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system.
- Subjects :
- Adenosine Triphosphate metabolism
Bacterial Outer Membrane Proteins genetics
Bacterial Outer Membrane Proteins metabolism
Chaperonins genetics
Chaperonins metabolism
Citric Acid Cycle
Complement Membrane Attack Complex genetics
Complement Membrane Attack Complex metabolism
Escherichia coli genetics
Escherichia coli growth & development
Escherichia coli Infections microbiology
Escherichia coli Proteins genetics
Escherichia coli Proteins metabolism
Humans
Purines biosynthesis
Complement System Proteins immunology
Escherichia coli metabolism
Escherichia coli Infections immunology
Glycine metabolism
Serine metabolism
Serum chemistry
Threonine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31346171
- Full Text :
- https://doi.org/10.1038/s41467-019-11129-5