Camel-Derived Nanobodies as Potent Inhibitors of New Delhi Metallo-β-Lactamase-1 Enzyme

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Abstract
The injudicious usage of antibiotics during infections caused by Gram-negative bacteria leads to the emergence of β-lactamases. Among them, the NDM-1 enzyme poses a serious threat to human health. Developing new antibiotics or inhibiting β-lactamases might become essential to reduce and prevent bacterial infections. Nanobodies (Nbs), the smallest antigen-binding single-domain fragments derived from Camelidae heavy-chain-only antibodies, targeting enzymes, are innovative alternatives to develop effective inhibitors. The biopanning of an immune VHH library after phage display has helped to retrieve recombinant antibody fragments with high inhibitory activity against recombinant-NDM-1 enzyme. Nb02NDM-1, Nb12NDM-1, and Nb17NDM-1 behaved as uncompetitive inhibitors against NDM-1 with Ki values in the nM range. Remarkably, IC50 values of 25.0 nM and 8.5 nM were noted for Nb02NDM-1 and Nb17NDM-1, respectively. The promising inhibition of NDM-1 by Nbs highlights their potential application in combating particular Gram-negative infections.
Funding Information
  • Ministry of High Education and Scientific Research of Tunisia (18PJEC06-06, PCI-36, PRF (D4P1), 2023)
  • Ministry of Health, Pasteur Institute of Tunis: Internal Collaborative Program (18PJEC06-06, PCI-36, PRF (D4P1), 2023)
  • Federative National Project (18PJEC06-06, PCI-36, PRF (D4P1), 2023)
  • Department of Biotechnological and Applied Clinical Sciences of the University of L’Aquila: intramural DISCAB (18PJEC06-06, PCI-36, PRF (D4P1), 2023)

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