title: Metabolic Mechanism for l-Leucine-Induced Metabolome To Eliminate Streptococcus iniae.
abstract: Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for l-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC-MS-based metabolomics was used to investigate the tilapia liver metabolic profile in the presence of exogenous l-leucine. Thirty-seven metabolites of differential abundance were determined, and 11 metabolic pathways were enriched. Pattern recognition analysis identified serine and proline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting that the two metabolites play crucial roles in l-leucine-induced elimination of the pathogen by the host. Exogenous l-serine reduces the mortality of tilapias infected by S. iniae, providing a robust proof supporting the conclusion. Furthermore, exogenous l-serine elevates expression of genes IL-1β and IL-8 in tilapia spleen, but not TNFα, CXCR4 and Mx, suggesting that the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that l-leucine promotes macrophages to kill both Gram-positive and Gram-negative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous l-leucine is partly attributed to elevation of l-serine. These results demonstrate a metabolic mechanism by which exogenous l-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens.
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Chao-Chao
authors.initials: CC
authors.lastname: Du
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.|Tibet Vocational Technical College , Lhasha 850000, People's Republic of China.
authors.forename: Man-Jun
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Min-Yi
authors.initials: MY
authors.lastname: Li
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Xuan-Xian
authors.identifier: 0000-0002-0200-1395
authors.initials: XX
authors.lastname: Peng
mesh_terms: D000818:Animals; D005393:Fish Diseases / Q000382:microbiology; D008401:Gas Chromatography-Mass Spectrometry; D007113:Immunity, Innate; D007930:Leucine / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D010587:Phagocytosis / Q000187:drug effects; D013154:Spleen / Q000378:metabolism; D013290:Streptococcal Infections; D013291:Streptococcus / Q000276:immunology*; D017210:Tilapia / Q000276:immunology / Q000378:metabolism*
chemical_list: D007930:Leucine
keywords: Streptococcus iniae; leucine; metabolic mechanism; metabolome; tilapia