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Metabolic mechanism of ceftazidime resistance in Vibrio alginolyticus

Shi-Rao Liu1, Xuan-Xian Peng1,2, 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, lihui32@sysu.edu.cn; pxuanx@sysu.edu.cn.

Infection and Drug Resistance
|March 14, 2019
PubMed
Abstract

Insights

Bacterial metabolism significantly impacts cephalosporin antibiotic effectiveness. This study reveals that altered metabolism, including inefficient respiration and pyruvate cycle, enhances resistance in Vibrio alginolyticus, offering new targets for combating antibiotic resistance.

Area of Science:

  • Microbiology
  • Metabolomics
  • Antimicrobial Resistance

Background:

  • Microbial metabolism influences antibiotic efficacy, yet its role in cephalosporin resistance in Vibrio spp. is understudied.
  • Vibrio species are significant pathogens in human and aquaculture settings.

Purpose of the Study:

  • To investigate the metabolome of cephalosporin antibiotic-resistant Vibrio alginolyticus.
  • To elucidate the contribution of bacterial metabolism to drug and multidrug resistance.

Main Methods:

  • Comparative metabolomic analysis of isogenic ceftazidime-resistant (VA-R_CAZ) and sensitive (VA-S) Vibrio alginolyticus strains.
  • Gas chromatography-mass spectrometry (GC-MS) was employed for metabolome profiling.

Main Results:

  • Resistant VA-R_CAZ exhibited inefficient respiration, an impaired pyruvate cycle, increased fatty acid biosynthesis, and reduced membrane proton motive force.
  • Inhibiting pyruvate cycle enzymes (furfural, malonate) increased antibiotic resistance, while inhibiting fatty acid synthesis (triclosan) decreased resistance.

Conclusions:

  • Bacterial metabolism plays a critical role in cephalosporin resistance in Vibrio species.
  • Understanding these metabolic mechanisms can inform strategies to combat antibiotic-resistant infections.
Keywords:
antibiotic resistancebiosynthesis of fatty acidscentral carbon metabolismcephalosporinmetabolomicspyruvate cycle

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