Research Article

Protein & Cell

, Volume 2, Issue 3, pp 250-258

First online:

An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamase II from Erythrobacter litoralis

  • Beiwen ZhengAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCollege of Life Sciences, Graduate University, Chinese Academy of Sciences
  • , Shuguang TanAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCollege of Life Sciences, Graduate University, Chinese Academy of Sciences
  • , Jia GaoAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesThe Key Laboratory of Ministry of Education for Microbial and Plant Genetic Engineering, Guangxi University
  • , Huiming HanAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCollege of Life Sciences, Graduate University, Chinese Academy of Sciences
  • , Jun LiuAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
  • , Guangwen LuAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCollege of Life Sciences, Graduate University, Chinese Academy of Sciences
  • , Di LiuAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesNetwork Information Center, Institute of Microbiology, Chinese Academy of Sciences
  • , Yong YiAffiliated withThe 306th Hospital of Chinese PLA
  • , Baoli ZhuAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    • , George F. GaoAffiliated withCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesCollege of Life Sciences, Graduate University, Chinese Academy of SciencesBeijing Institutes of Life Science, Chinese Academy of Sciences Email author 

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Abstract

NDM-1 (New Delhi metallo-beta-lactamase) gene encodes a metallo-beta-lactamase (MBL) with high carbapenemase activity, which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern. Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis, a marine microbial isolate. We have further expressed these two mature proteins in E. coli cells, both of which present as a monomer with a molecular mass of 25 kDa. Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline. The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance, Zn2+-bound NDM-1, adopts at least some stable tertiary structure in contrast to the metal-free protein. Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic, challenging the antimicrobial resistance monitoring.

Keywords

NDM-1 metallo-β-lactamase Erythrobacter litoralis similarity antibiotics resistance