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

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-induce...

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Bibliographic Details
Published in:Virulence 2021-12, Vol.12 (1), p.1737-1753
Main Authors: Kuang, Su-fang, Chen, Yue-tao, Chen, Jia-jie, Peng, Xuan-xian, Chen, Zhuanggui, Li, Hui
Format: Article
Language:English
Subjects:
Ala
Alanine - pharmacology
Anti-Bacterial Agents - pharmacology
Arginine
Drug Resistance, Bacterial
Drug Synergism
Gent
Gentamicins - pharmacology
Homicide
metabolomics
Nitric Oxide
Nitric Oxide Synthase
NOS
Research Paper
V. alginolyticus
Vibrio alginolyticus - drug effects
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Summary: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.
ISSN:2150-5594
2150-5608
DOI:10.1080/21505594.2021.1947447