PUBLICATION
Reduced redox-dependent mechanism and glucose-mediated reversal in gentamicin-resistant Vibrio alginolyticus
- Authors
- Zhang, S., Wang, J., Jiang, M., Xu, D., Peng, B., Peng, X.X., Li, H.
- ID
- ZDB-PUB-191011-15
- Date
- 2019
- Source
- Environmental microbiology 21(12): 4724-4739 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/metabolism
- Anti-Bacterial Agents/pharmacology*
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism
- Biological Transport
- Drug Resistance, Bacterial*
- Electron Transport Complex I/genetics
- Electron Transport Complex I/metabolism
- Gentamicins/metabolism
- Gentamicins/pharmacology*
- Glucose/metabolism*
- Oxidation-Reduction
- Vibrio/metabolism
- Vibrio alginolyticus/drug effects
- Vibrio alginolyticus/genetics
- Vibrio alginolyticus/metabolism*
- PubMed
- 31595636 Full text @ Environ. Microbiol.
Citation
Zhang, S., Wang, J., Jiang, M., Xu, D., Peng, B., Peng, X.X., Li, H. (2019) Reduced redox-dependent mechanism and glucose-mediated reversal in gentamicin-resistant Vibrio alginolyticus. Environmental microbiology. 21(12):4724-4739.
Abstract
Strategy of managing antibiotic-resistant Vibrio alginolyticus, a bacterial pathogen that threatens human health and animal farming, is not available due to the lack of knowledge about the underlying mechanism of antibiotic resistance. Here, we showed that gentamicin-resistant V. alginolyticus (VA-RGEN ) has four mutations on metabolism and one mutation on a two-component system by whole-genome and PCR-based sequencing, indicating the metabolic shift in VA-RGEN. Thus, metabolic profile was investigated by GC-MS based metabolomics. Glucose was identified as a crucial biomarker, whose abundance was decreased in VA-RGEN . Further analysis with iPath, and gene expression and enzyme activity of the pyruvate cycle (the P cycle) demonstrated a global depressed metabolic pathway network in VA-RGEN . Consistently, NADH, sodium-pumping NADH:ubiquinone oxidoreductase (Na(+)-NQR) system, membrane potential, and intracellular gentamicin were decreased in VA-RGEN . These findings indicate the reduced redox state contributes to antibiotic resistance. Interestingly, exogenous glucose potentiated gentamicin to efficiently kill VA-RGEN through the promotion of the P cycle, NADH, membrane potential, and intracellular gentamicin. The potentiation was further confirmed in a zebrafish model. These results indicate that the gentamicin resistance reduces the P cycle and Na(+)-NQR system and thereby decreases redox state, membrane potential, and gentamicin uptake, which can be reversed by exogenous glucose. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping