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

Small, soluble single-domain fragments derived from the unique variable reg ion of dromedary heavy-chain antibodies (VHHs) against enzymes are known to be potent inhibitors. The immunization of dromedaries with the TEM-1 and B ell beta -lactamases has lead to the isolation of such single-domain antibo dy 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% inh ibitory 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 bacte ria, leads to a higher ampicillin sensitivity of the bacteria. This innovat ive strategy could generate multiple potent inhibitors for all types of bet a -lactamases.