Camel-Derived Nanobodies as Potent Inhibitors of New Delhi Metallo-β-Lactamase-1 Enzyme
Rahma Ben Abderrazek,
Emna Hamdi,
Alessandra Piccirilli,
Sayda Dhaouadi,
Serge Muyldermans,
Mariagrazia Perilli,
Balkiss Bouhaouala-Zahar
Affiliations
Rahma Ben Abderrazek
Laboratoire des Biomolécules Venins et Applications Théranostiques, Institut Pasteur Tunis, 13 Place Pasteur, Tunisie Université Tunis El Manar, B.P N 93, Tunis 1068, Tunisia
Emna Hamdi
Laboratoire des Biomolécules Venins et Applications Théranostiques, Institut Pasteur Tunis, 13 Place Pasteur, Tunisie Université Tunis El Manar, B.P N 93, Tunis 1068, Tunisia
Alessandra Piccirilli
Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi dell’Aquila, Via Veteoio Coppito, 67100 L’Aquila, Italy
Sayda Dhaouadi
Laboratoire des Biomolécules Venins et Applications Théranostiques, Institut Pasteur Tunis, 13 Place Pasteur, Tunisie Université Tunis El Manar, B.P N 93, Tunis 1068, Tunisia
Serge Muyldermans
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleenlaan, 9, 1050 Brussels, Belgium
Mariagrazia Perilli
Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi dell’Aquila, Via Veteoio Coppito, 67100 L’Aquila, Italy
Balkiss Bouhaouala-Zahar
Laboratoire des Biomolécules Venins et Applications Théranostiques, Institut Pasteur Tunis, 13 Place Pasteur, Tunisie Université Tunis El Manar, B.P N 93, Tunis 1068, Tunisia
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.
