Abstract:
:Staphylococcus aureus is a notorious bacterial pathogen that often causes soft tissue and bloodstream infections and invariably garners resistance mechanisms against new antibiotics. Modulation of the host immune response by metabolites is a powerful tool against bacterial infections, but has not yet been used against S. aureus infections. In this study, we identified four metabolite biomarkers: L-proline, L-isoleucine, L-leucine, and L-valine (PILV), through a metabolomics study using animal models of S. aureus bloodstream infection. The exogenous administration of each metabolite or of PILV showed anti-infective effects, and a higher protection was achieved with PILV in comparison to individual metabolites. During the staphylococcal infection, the expression of most host arginase and nitric oxide synthase (NOS) isozymes was simultaneously induced in mouse liver, kidney, and blood samples. However, the induction of arginase isozymes was dramatically stronger than that of NOS isozymes. This elevated arginase activity was inhibited by the metabolite biomarkers thus killing S. aureus, and PILV exhibited the strongest inhibition of arginase activity and bacterial inhibition. The suppression of arginase activity also contributed to the metabolite-mediated phagocytic killing of S. aureus in mouse and human blood. Our findings demonstrate the metabolite-mediated arginase inhibition as a therapeutic intervention for S. aureus infection.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Pang R,Zhou H,Huang Y,Su Y,Chen Xdoi
10.3389/fimmu.2020.01639subject
Has Abstractpub_date
2020-07-28 00:00:00pages
1639issn
1664-3224journal_volume
11pub_type
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journal_title:Frontiers in immunology
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章,多中心研究
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pub_type: 已发布勘误
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