Development of Nanobodies as Theranostic Agents against CMY-2-Like Class C b-Lactamases

[en] Three soluble single-domain fragments derived from the unique variable region of camelid heavy-chain antibodies (VHHs) against the CMY-2 b-lactamase behaved as inhibitors. The structure of the complex VHH cAbCMY-2(254)/CMY-2 showed that the epitope is close to the active site and that the CDR3 of the VHH protrudes into the catalytic site. The b-lactamase inhibition pattern followed a mixed profile with a predominant noncompetitive component. The three isolated VHHs recognized overlapping epitopes since they behaved as competitive binders. Our study identified a binding site that can be targeted by a new class of b-lactamase inhibitors designed on the sequence of the paratope. Furthermore, the use of mono- or bivalent VHH and rabbit polyclonal anti- CMY-2 antibodies enables the development of the first generation of enzyme-linked immunosorbent assay (ELISA) for the detection of CMY-2 produced by CMY-2-expressing bacteria, irrespective of resistotype.

Disciplines :

Veterinary medicine & animal health

Author, co-author :

Cawez, Frédéric ; Université de Liège - ULiège > Integrative Biological Sciences (InBioS)

Mercuri, Paola ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques

Morales Yánez, Francisco Javier ; Université de Liège - ULiège > Integrative Biological Sciences (InBioS)

Maalouf, Rita ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines

Vandevenne, Marylène ; Université de Liège - ULiège > Integrative Biological Sciences (InBioS)

Kerff, Frédéric ; Université de Liège - ULiège > Département des sciences de la vie > Centre d'Ingénierie des Protéines (CIP)

Guérin, Virginie ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire

Mainil, Jacques ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI)

Thiry, Damien ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Bactériologie vétérinaire et maladies bactériennes animales

Saulmont, Marc

More authors (6 more)

Language :

English

Title :

Development of Nanobodies as Theranostic Agents against CMY-2-Like Class C b-Lactamases

Publication date :

2023

Journal title :

Antimicrobial Agents and Chemotherapy

ISSN :

0066-4804

eISSN :

1098-6596

Publisher :

American Society for Microbiology, Washington, United States - District of Columbia

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://journals.asm.org/journal/aac

Data Set :

10.1128/aac.01499-22

Available on ORBi :

since 11 May 2023

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