Molecular Basis of NDM-1, a New Antibiotic Resistance Determinant
2011

Understanding NDM-1: A New Antibiotic Resistance Mechanism

publication Evidence: moderate

Author Information

Author(s): Liang Zhongjie, Li Lianchun, Wang Yuanyuan, Chen Limin, Kong Xiangqian, Hong Yao, Lan Lefu, Zheng Mingyue, Guang-Yang Cai, Liu Hong, Shen Xu, Luo Cheng, Li Keqin Kathy, Chen Kaixian, Jiang Hualiang

Primary Institution: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Hypothesis

What is the molecular basis for the antibiotic resistance of NDM-1?

Conclusion

The study reveals that NDM-1 is highly resistant to carbapenems and cephalosporins, while being susceptible to aztreonam and tigecycline.

Supporting Evidence

  • NDM-1 can hydrolyze carbapenem antibiotics like meropenem and imipenem.
  • The study identified tigecycline as a weak inhibitor of NDM-1.
  • Mutagenesis experiments confirmed the importance of specific residues for NDM-1 activity.

Takeaway

NDM-1 is a superbug that can break down many antibiotics, making it hard to treat infections. This study helps us understand how it works so we can find new medicines.

Methodology

The study used homology modeling and molecular docking to analyze the structure of NDM-1 and its interactions with antibiotics, followed by biological experiments to validate the findings.

Limitations

The study primarily focuses on in vitro experiments, which may not fully represent in vivo conditions.

Digital Object Identifier (DOI)

10.1371/journal.pone.0023606

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