[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
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