Loss in the Antibacterial Ability of a PyrR Gene Regulating Pyrimidine Biosynthesis after Using CRISPR/Cas9-Mediated Knockout for Metabolic Engineering in Lactobacillus casei

文献类型： 外文期刊

第一作者： Chen, Shaojun

作者： Chen, Shaojun;Qin, Ziliang;Li, Gang;Tian, Yaguang;Liu, Di;Jiang, Xinpeng;He, Xinmiao;Wang, Wentao;Liu, Di;Nai, Zida

作者机构：

关键词： CRISPR/Cas9; Lactobacillus casei; PyrR; pyrimidine biosynthesis

期刊名称：MICROORGANISMS （ 影响因子：4.5； 五年影响因子：4.8 ）

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年卷期： 2023 年 11 卷 10 期

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收录情况： SCI

摘要： Lactobacillus casei (L. casei) has four possible mechanisms: antimicrobial antagonism, competitional adhesion, immunoregulation, and the inhibition of bacterial toxins. To delineate the metabolic reactions of nucleotides from L. casei that are associated with mechanisms of inhibiting pathogens and immunoregulation, we report that a PyrR-deficient L. casei strain was constructed using the CRISPR-Cas9(D10A) tool. Furthermore, there were some changes in its basic biological characterization, such as its growth curve, auxotroph, and morphological damage. The metabolic profiles of the supernatant between the PyrR-deficient and wild strains revealed the regulation of the synthesis of genetic material and of certain targeting pathways and metabolites. In addition, the characteristics of the PyrR-deficient strain were significantly altered as it lost the ability to inhibit the growth of pathogens. Moreover, we identified PyrR-regulating pyrimidine biosynthesis, which further improved its internalization and colocalization with macrophages. Evidence shows that the PyrR gene is a key active component in L. casei supernatants for the regulation of pyrimidine biosynthesis against a wide range of pathogens.

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