title: GC-MS-Based Metabolome and Metabolite Regulation in Serum-Resistant Streptococcus agalactiae.
abstract: Streptococcus agalactiae causes severe systemic infections in human and fish. In the present study, we established a pathogen-plasma interaction model by which we explored how S. agalactiae evaded serum-mediated killing. We found that S. agalactiae grew faster in the presence of yellow grouper plasma than in the absence of the plasma, indicating S. agalactiae evolved a way of evading the fish immune system. To determine the events underlying this phenotype, we applied GC-MS-based metabolomics approaches to identify differential metabolomes between S. agalactiae cultured with and without yellow grouper plasma. Through bioinformatics analysis, decreased malic acid and increased adenosine were identified as the most crucial metabolites that distinguish the two groups. Meanwhile, they presented with decreased TCA cycle and elevated purine metabolism, respectively. Finally, exogenous malic acid and adenosine were used to reprogram the plasma-resistant metabolome, leading to elevated and decreased susceptibility to the plasma, respectively. Therefore, our findings reveal for the first time that S. agalactiae utilizes a metabolic trick to respond to plasma killing as a result of serum resistance, which may be reverted or enhanced by exogenous malic acid and adenosine, respectively, suggesting that the metabolic trick can be regulated by metabolites.
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquatic Food Safety, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquatic Food Safety, 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 Bio-Control, MOE Key Lab Aquatic Food Safety, 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 Bio-Control, MOE Key Lab Aquatic Food Safety, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Zhi-Xue
authors.initials: ZX
authors.lastname: Cheng
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Bio-Control, MOE Key Lab Aquatic Food Safety, 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 Bio-Control, MOE Key Lab Aquatic Food Safety, School of Life Sciences, Sun Yat-sen University , University City, Guangzhou 510006, People's Republic of China.
authors.forename: Xuan-Xian
authors.initials: XX
authors.lastname: Peng
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D002952:Citric Acid Cycle; D019295:Computational Biology; D005399:Fishes / Q000276:immunology* / Q000382:microbiology; D008401:Gas Chromatography-Mass Spectrometry; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D008293:Malates / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D011687:Purines / Q000378:metabolism; D044967:Serum / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*
chemical_list: D008293:Malates; D011687:Purines; C030298:malic acid; D000241:Adenosine; C030985:purine
keywords: Streptococcus agalactiae; grouper; reprogramming metabolomics; serum resistance