Background: Microbial metabolism confounds antibiotic efficacy. However, information regarding effect of metabolism on cephalosporin antibiotics-mediated killing and Vibrio spp  is largely absence, although the drugs are widely used in clinic and the bacteria are pathogens to both human and aquaculture animals. 
Purpose: This study explores the metabolome of cephalosporin antibiotic-resistant Vibrio alginolyticus  and analyzes the role of bacterial metabolism in drug and multidrug-resistance.
Results: The metabolomes of isogenic ceftazidime-resistant V. alginolyticus  (VA-R_CAZ) and ceftazidime-sensitive V. alginolyticus  (VA-S) were analyzed using gas chromatography -mass spectrometry. The metabolome of VA-R_CAZ is characterized by inefficient respiration, an inefficient pyruvate cycle (P cycle), increased biosynthesis of fatty acids and decreased membrane proton motive force. This hypothesis was confirmed by the fact that furfural and malonate, inhibitors of pyruvate dehydrogenase and succinate dehydrogenase (P cycle enzymes), respectively, increased resistance of VA-R_CAZ to antibiotics, while exposure to triclosan, to inhibit biosynthesis of fatty acids, decreased resistance.
Conclusion: These results contribute to our understanding of mechanisms of bacterial antibiotic-resistance and may lead to more effective approaches to treat, manage or prevent infections caused by antibiotic-resistant pathogens including those of the Vibrio  species.
Keywords: antibiotic resistance, cephalosporin, central carbon metabolism, pyruvate cycle, biosynthesis of fatty acids, metabolomics