Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae.

Amino Acid Sequence; Ampicillin/pharmacology; Animals; Antibody Specificity; Bacterial Proteins/pharmacology; Camels/immunology; Escherichia coli/drug effects/enzymology; Immunoglobulin Fragments/isolation & purification/pharmacology; Male; Molecular Sequence Data; Penicillin Resistance; Penicillins/pharmacology; Protein Structure, Tertiary; Sequence Homology, Amino Acid; beta-Lactamases/antagonists & inhibitors/immunology

Abstract :

[en] Small, soluble single-domain fragments derived from the unique variable region of dromedary heavy-chain antibodies (VHHs) against enzymes are known to be potent inhibitors. The immunization of dromedaries with the TEM-1 and BcII beta-lactamases has lead to the isolation of such single-domain antibody fragments specifically recognizing and inhibiting those beta-lactamases. Two VHHs were isolated that inhibit TEM-1 and one BcII inhibiting VHH was identified. All inhibitory VHHs were tight-binding inhibitors. The 50% inhibitory concentrations were determined for all inhibitors and they were all in the same range as the enzyme concentration used in the assay. Addition of the VHHs to the TEM-1 beta-lactamase, expressed on the surface of bacteria, leads to a higher ampicillin sensitivity of the bacteria. This innovative strategy could generate multiple potent inhibitors for all types of beta-lactamases.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Conrath, K. E.; Vrije Universiteit Brussel - VUB > Ultrastructure

Lauwereys, M.

Galleni, Moreno ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques, Centre d'Ingénierie des Protéines

Matagne, André ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie, Centre d'Ingénierie des Protéines

Frère, Jean-Marie ; Université de Liège - ULiège > Centre d'ingénierie des protéines

Kinne, J.

Wyns, L.

Muyldermans, S.; Vrije Universiteit Brussel - VUB > Ultrastructure

Language :

English

Title :

Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae.

Publication date :

2001

Journal title :

Antimicrobial Agents and Chemotherapy

ISSN :

0066-4804

eISSN :

1098-6596

Publisher :

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

Volume :

Issue :

Pages :

2807-12

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 23 November 2009

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Scopus citations^®

311

Scopus citations^®
without self-citations

235

OpenCitations

250

OpenAlex citations

332

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