β-lactamase inhibitors derived from single-domain antibody fragments elicited in the Camelidae

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 Bell 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 Bell 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-I 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.