CHARACTERIZATION OF BETA-LACTAMASES IN MYCOBACTERIUM-FORTUITUM INCLUDING A ROLE IN BETA-LACTAM RESISTANCE AND EVIDENCE OF PARTIAL INDUCIBILITY

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Abstract
The .beta.-lactamases from the 3 biovariants of M. fortuitum were compared on the basis of substrate profiles, susceptibility to enzyme inhibitors, and inducibility in the presence of selected .beta.-lactams. Despite differences in the distribution of .beta.-lactamase bands observed when enzymes from different isolates were subjected to isoelectric focusing, substrate profiles for the 3 biovariants were similar. All demonstrated a comparable broad spectrum hydrolytic activity for both cephalosporins and penicillins. The MIC for amoxicillin were reduced 4- to 16-fold when combined with the .beta.-lactamase inhibitorclavulanic acid, but not to a clinically susceptible of enzyme to inhibition by clavulanic acid as determnied in an in vitro assay. Although all M. fortuitum strains produce .beta.-lactamase under routine growth conditions, 90% of strains demonstrated an increase in the amount of this enzyme when cultured in the presence of selected .beta.-lactams as potential inducers. Quantitative assays and isoelectric focusing further indicated that this apparent induction of .beta.-lactamase is a simple enhancement of the same enzyme(s) produced in the absence of a known inducer. This is the first demonstration of any inducibility among mycobacterial .beta.-lactamases and suggests that synthesis of these enzymes in M. fortuitum is under some form of regulatory control. These results indicate that the .beta.-lactamases have a role in resistance of M. fortuitum to the .beta.-lactams. Other factors, such as permeability and penicillin-binding proteins, were not evaluated.