Synergy of alanine and gentamicin to reduce nitric oxide for elevating killing efficacy to antibiotic-resistant Vibrio alginolyticus.
Synergy of alanine and gentamicin to reduce nitric oxide for elevating killing efficacy to antibiotic-resistant Vibrio alginolyticus.
复制标题
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
DOI：
10.1080/21505594.2021.1947447
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Kuang SF;Chen YT;Chen JJ;Peng XX;Chen ZG;Li H
摘要本研究探讨了丙氨酸(ALA)和庆大霉素(Gent)在外源ALA增强Gent杀灭耐药溶藻弧菌代谢机制中的协同作用。为了验证这一点，基于GC-MS的代谢组学被用来表征ALA、Gent和两者诱导的代谢谱，确定一氧化氮(NO)的产生途径是了解代谢机制的最关键线索。银杏叶提取物、丙氨酸和两者均可导致大鼠血清总一氧化氮合酶(TNOS)活性降低，NO水平降低。NOS促进剂L-精氨酸和抑制剂NG-单甲基-L-精氨酸分别抑制和促进了细胞的杀伤，并使其活性和NO水平分别升高和降低。本研究进一步表明，CysJ是溶藻弧菌中产生NO的酶。这些结果表明，ALA和Gent的协同作用导致了最低的NO，这在ALA增强的Gent介导的杀伤中起着关键作用。
ABSTRACT The present study explored the cooperative effect of both alanine (Ala) and gentamicin (Gent) on metabolic mechanisms by which exogenous Ala potentiates Gent to kill antibiotic-resistant Vibrio alginolyticus. To test this, GC-MS-based metabolomics was used to characterize Ala-, Gent- and both-induced metabolic profiles, identifying nitric oxide (NO) production pathway as the most key clue to understand metabolic mechanisms. Gent, Ala and both led to low, lower and lowest activity of total nitric oxide synthase (tNOS) and level of NO, respectively. NOS promoter L-arginine and inhibitor NG-Monomethyl-L-arginine inhibited and promoted the killing, respectively, with the elevation and decrease of NOS activity and NO level. The present study further showed that CysJ is the enzyme-producing NO in V. alginolyticus. These results indicate that the cooperative effect of Ala and Gent causes the lowest NO, which plays a key role in Ala-potentiated Gent-mediated killing.
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