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Antimicrobial Agents and Chemotherapy, October 2001, p. 2807-2812, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2807-2812.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

beta -Lactamase Inhibitors Derived from Single-Domain Antibody Fragments Elicited in the Camelidae

Katja E. Conrath,1,* Marc Lauwereys,1 Moreno Galleni,2 André Matagne,2 Jean-Marie Frère,2 Jörg Kinne,3 Lode Wyns,1 and Serge Muyldermans1

Department of Ultrastructure, Vrije Universiteit Brussel, B-1640 St. Genesius Rode,1 and Institut de Chimie, Centre d'Ingénerie des Protéines, Université de Liège, B-4000 Sart-Tilman, Liège,2 Belgium, and Central Veterinary Research Laboratories, Dubai, United Arab Emirates3

Received 10 January 2001/Returned for modification 8 May 2001/Accepted 27 July 2001

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.

* Corresponding author. Mailing address: Department Ultrastructure, Vrije Universiteit Brussel, Pardenstraat 65, B-1640 St. Genesius Rode, Belgium. Phone: 32/2/35 90 282. Fax: 32/2/35 90 289. E-mail: kconrath{at}vub.ac.be.

Antimicrobial Agents and Chemotherapy, October 2001, p. 2807-2812, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2807-2812.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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