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代谢组学分析在辅助理解不同李斯特菌谱系和血清型致病性中的应用。

Application of metabolomics analysis to aid in understanding the pathogenicity of different lineages and different serotypes of Listeria monocytogenes.

机构信息

College of Food Science and Engineering, Nanjing University of Finance and Economics, 210023, China; Chinese Academy of Inspection and Quarantine, No.11, Ronghua South Street, Daxing District, Beijing 100176, China.

Chinese Academy of Inspection and Quarantine, No.11, Ronghua South Street, Daxing District, Beijing 100176, China.

出版信息

Int J Food Microbiol. 2022 Jul 16;373:109694. doi: 10.1016/j.ijfoodmicro.2022.109694. Epub 2022 Apr 29.

DOI:10.1016/j.ijfoodmicro.2022.109694
PMID:35580408
Abstract

Listeria monocytogenes is a foodborne pathogen with high mortality in young children, elderly persons, pregnant women, and immune-compromised individuals. Most human listeriosis cases are associated with four serotypes (1/2a, 1/2b, 1/2c and 4b) within lineages I and II. The intracellular metabolic changes in L. monocytogenes from different lineages and serotypes remain unclear. Here, a non-targeted metabolomics strategy, based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with chemometrics was performed to analyze the metabolic fluctuations in the lineages and serotypes of L. monocytogenes. In the aggregate, 93 L. monocytogenes isolates (two lineages and four serotypes) were investigated, and a total of 48 differential biomarker metabolites were identified. Twenty differential metabolites were observed at the lineage level, while the others were found at the serotype level. At the lineage level, significantly lower contents (fold change [FC] = 3.60) of γ-aminobutyric acid (GABA) was found in lineage II strains, as compared to lineage I strains. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis showed that different substances between lineages I and II participated in multiple metabolic pathways, among which pyrimidine metabolism, purine metabolism, and aminoacyl-tRNA biosynthesis were significantly enriched. The major significantly upregulated (P < 0.05) metabolites, including uridine 5'-monophosphate, uridine, guanosine monophosphate, and guanosine, in lineage II strains affect the synthesis of DNA and RNA. At the serotype level, the upregulation of urea precursor substances produced by the purine metabolism pathway in serotype 4b strains may be one reason for the increased virulence of serotype 4b strains, compared to other serotype strains. In addition, the upregulation of pyridoxine in the vitamin B6 pathway in 4b strains was also observed. The differential metabolic pathway of 1/2a and 1/2c strains is nucleotide metabolism, which could lead to differences in the biosynthesis of DNA and RNA of the strain and further affect the growth and proliferation of strains.

摘要

李斯特菌是一种食源性病原体,对幼儿、老年人、孕妇和免疫功能低下者的死亡率较高。大多数人类李斯特菌病与谱系 I 和 II 中的四个血清型(1/2a、1/2b、1/2c 和 4b)有关。不同谱系和血清型李斯特菌的细胞内代谢变化尚不清楚。在这里,采用基于超高效液相色谱四极杆飞行时间质谱联用(UPLC-QTOF-MS)和化学计量学的非靶向代谢组学策略,分析了李斯特菌谱系和血清型的代谢波动。总共研究了 93 株李斯特菌(两个谱系和四个血清型),共鉴定出 48 种差异生物标志物代谢物。在谱系水平上观察到 20 种差异代谢物,而其他代谢物则在血清型水平上发现。在谱系水平上,与谱系 I 菌株相比,谱系 II 菌株中 γ-氨基丁酸(GABA)的含量明显较低(倍数变化 [FC] = 3.60)。京都基因与基因组百科全书(KEGG)途径富集分析表明,谱系 I 和 II 之间的不同物质参与了多种代谢途径,其中嘧啶代谢、嘌呤代谢和氨酰-tRNA 生物合成明显富集。谱系 II 菌株中主要显著上调(P < 0.05)的代谢物,包括尿苷 5'-单磷酸、尿苷、鸟苷单磷酸和鸟苷,影响 DNA 和 RNA 的合成。在血清型水平上,与其他血清型菌株相比,血清型 4b 菌株嘌呤代谢途径中尿素前体物质的上调可能是 4b 血清型菌株毒力增加的原因之一。此外,还观察到 4b 株中维生素 B6 途径中吡哆醇的上调。1/2a 和 1/2c 菌株的差异代谢途径是核苷酸代谢,这可能导致菌株 DNA 和 RNA 生物合成的差异,并进一步影响菌株的生长和增殖。

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