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Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing
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Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing
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Journal Article
Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing
2019
Overview
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.
Serum-resistant bacteria can escape complement killing in the bloodstream. Here, using metabolomics and metabolite perturbations, the authors describe an altered metabolic state in serum-resistant
Escherichia coli
and show that exogenous glycine potentiates elimination of pathogenic bacteria in vivo.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/88
/ 631/114
/ 631/326
/ 631/45
/ 64/60
/ 96
/ 96/31
/ Adenosine Triphosphate - metabolism
/ ATP
/ Bacteria
/ Bacterial Outer Membrane Proteins - genetics
/ Bacterial Outer Membrane Proteins - metabolism
/ Complement Membrane Attack Complex - genetics
/ Complement Membrane Attack Complex - metabolism
/ Complement System Proteins - immunology
/ E coli
/ Escherichia coli - growth & development
/ Escherichia coli - metabolism
/ Escherichia coli Infections - immunology
/ Escherichia coli Infections - microbiology
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Glycine
/ Humanities and Social Sciences
/ Humans
/ Immunity
/ Proteins
/ Science
/ Serine
