4.5 Article

Synergy of alanine and gentamicin to reduce nitric oxide for elevating killing efficacy to antibiotic-resistant Vibrio alginolyticus

期刊

VIRULENCE
卷 12, 期 1, 页码 1737-1753

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/21505594.2021.1947447

关键词

V; alginolyticus; Ala; Gent; nitric oxide; NOS; metabolomics

资金

  1. Science and technology project of Guangzhou [201904020042]
  2. NSFC project [31772888]
  3. National Key Research and Development Program of China [2018YFD0900504]

向作者/读者索取更多资源

The study found that the cooperative effect of alanine and gentamicin can reduce the level of nitric oxide, which plays a key role in the process of alanine-potentiated gentamicin killing.
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 N-G-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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