Structure, evolution and virtual screening of NDM-1 strain from Kolkata

Area of Science:

• Microbiology
• Biochemistry
• Drug Discovery

Background:

• Beta-lactam antibiotics are crucial for treating bacterial infections.
• Beta-lactamase enzymes, like New Delhi Metallo-β-lactamase (NDM-1), confer bacterial resistance to these vital antibiotics.
• NDM-1 resistance necessitates the development of new therapeutic strategies and compounds.

Purpose of the Study:

• To investigate the structural characteristics of NDM-1.
• To identify potential compounds with binding affinity to NDM-1.
• To understand the evolutionary convergence of NDM-1 strains.

Main Methods:

• Molecular modeling of the NDM-1 structure.
• Analysis of evolutionary convergence in NDM-1 producing strains.
• In silico screening of antibiotic binding affinities to the modelled NDM-1.

Main Results:

• The modelled NDM-1 structure features an α-β-α barrel-type domain and a Zn metallo-β-lactamase N-terminal domain.
• NDM-1 from Kolkata demonstrated convergent evolution with other NDM-1 strains.
• Several antibiotics, including cephalosporins, ceftaroline, ceftobiprole, piperacillin, penamecillin, azidocillin, cefonicid, tigecycline, and colistin, exhibited significant binding affinity to the modelled NDM-1.

Conclusions:

• The structural insights into NDM-1 provide a basis for designing novel inhibitors.
• Certain existing antibiotics show potential for repurposing or as leads for new drug development against NDM-1 resistant bacteria.
• Understanding NDM-1 evolution aids in tracking and combating antibiotic resistance.