Infection and Drug Resistance (Feb 2019)
Metabolic mechanism of ceftazidime resistance in Vibrio alginolyticus
Abstract
Shi-Rao Liu,1 Xuan-Xian Peng,1,2 Hui Li1 1Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, Guangdong Province Key Laboratory for Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, People’s Republic of China; 2Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, People’s Republic of China 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-RCAZ) and ceftazidime-sensitive V. alginolyticus (VA-S) were analyzed using gas chromatography -mass spectrometry. The metabolome of VA-RCAZ 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-RCAZ 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
