Functional proteomics identify mannitol metabolism in serum resistance and therapeutic implications in Vibrio alginolyticus.
Functional proteomics identify mannitol metabolism in serum resistance and therapeutic implications in Vibrio alginolyticus.
复制标题
功能蛋白质组学鉴定溶藻弧菌血清抗性中的甘露醇代谢及其治疗意义
DOI：
10.3389/fimmu.2022.1010526
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
Peng, Bo
中科院分区：
文献类型：
--
作者：
Kou, Tian-shun;Wu, Jia-han;Chen, Xuan-wei;Peng, Bo
血清抗性被认为是细菌病原体最重要的致病特性之一，目前尚无有效的防控措施。我们之前发现，致病性大肠杆菌通过抑制甘氨酸、丝氨酸和苏氨酸代谢来获得血清抗性，而外源性甘氨酸重新激活该代谢途径可恢复其血清敏感性。基于此，我们进一步探究了甘氨酸在溶藻弧菌中发挥作用的潜在机制。因此，我们用甘氨酸处理溶藻弧菌，并采用基于串联质量标签的定量蛋白质组学技术分析其蛋白质组变化。与对照组相比，甘氨酸处理影响了总共291种蛋白质的表达。其中，由N646_0992编码的一种带有周质成分的陷阱型甘露醇/氯代芳香族化合物转运系统是表达量增加最为显著的蛋白质。结合通路富集分析显示果糖和甘露醇代谢发生改变，甘露醇成为增强血清杀菌活性的一种潜在代谢物。为证实这一点，外源性甘露醇降低了细菌活力。这种协同效应在溶藻弧菌 - 斑马鱼感染模型中得到进一步验证。此外，甘露醇增强血清杀菌作用的机制依赖于糖酵解和丙酮酸循环，这会增加补体成分C3b和C5b - 9在细菌表面的沉积，而抑制糖酵解或丙酮酸循环则会显著削弱这种协同效应及补体沉积。这些数据共同表明，甘露醇是一种能够逆转溶藻弧菌血清抗性的强效代谢物，在水产养殖中具有广阔的应用前景。
Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous discovery that pathogenic Escherichia coli represses glycine, serine, and threonine metabolism to confer serum resistance and that the reactivation of this pathway by exogenous glycine could restore serum sensitivity, we further investigate the mechanism underlying the action of glycine in Vibrio alginolyticus. Thus, V. alginolyticus is treated with glycine, and the proteomic change is profiled with tandem mass tag-based quantitative proteomics. Compared to the control group, glycine treatment influences the expression of a total of 291 proteins. Among them, a trap-type mannitol/chloroaromatic compound transport system with periplasmic component, encoded by N646_0992, is the most significantly increased protein. In combination with the pathway enrichment analysis showing the altered fructose and mannitol metabolism, mannitol has emerged as a possible metabolite in enhancing the serum killing activity. To demonstrate this, exogenous mannitol reduces bacterial viability. This synergistic effect is further confirmed in a V. alginolyticus–Danio rerio infection model. Furthermore, the mechanism underlying mannitol-enabled serum killing is dependent on glycolysis and the pyruvate cycle that increases the deposition of complement components C3b and C5b-9 on the bacterial surface, whereas inhibiting glycolysis or the pyruvate cycle significantly weakened the synergistic effects and complement deposition. These data together suggest that mannitol is a potent metabolite in reversing the serum resistance of V. alginolyticus and has promising use in aquaculture.
登录
查看更多内容
果糖促进鲫鱼抵抗嗜水气单胞菌感染的存活
影响因子：
7.3
作者：
Cao Y;Kou T;Peng L;Munang'andu HM;Peng B
通讯作者：
Peng B
影响因子：
6.4
作者：
Coggon CF;Jiang A;Goh KGK;Henderson IR;Schembri MA;Wells TJ
通讯作者：
Wells TJ
琥珀酸和肌苷协调对细菌感染的先天免疫反应。
影响因子：
6.7
作者：
通讯作者：
--
丙氨酸和庆大霉素协同减少一氧化氮，提高对耐抗生素溶藻弧菌的杀灭效果
影响因子：
5.2
作者：
Kuang SF;Chen YT;Chen JJ;Peng XX;Chen ZG;Li H
通讯作者：
Li H
迟缓爱德华氏菌调节三羧酸循环以逃避补体介导的杀伤
影响因子：
7.3
作者：
Cheng ZX;Gong QY;Wang Z;Chen ZG;Ye JZ;Li J;Wang J;Yang MJ;Ling XP;Peng B
通讯作者：
Peng B