A SILENT CARBAPENEMASE GENE IN STRAINS OF BACTEROIDES-FRAGILIS CAN BE EXPRESSED AFTER A ONE-STEP MUTATION

High-level carbapenem-resistant (Cpm(R)) mutants, with MICs for imipenem and carbapenem of > 128-mu-g/ml, were selected in vitro from four carbapenem-susceptible (Cpm(s)) clinical isolates of Bacteroides fragilis. The Cpm(s) strains produced very tow levels of beta-lactamase activity, which was increased approx. 50- to 100-fold in the Cpm(R) mutants. Isoclectric focussing and enzyme kinetic analysis (K(m) and V(rel)) of the 'carbapenemases' from the Cpm(R) mutants and similarly resistant clinical isolates suggested a close relatedness of the enzymes. A probe covering most of the cfiA gene encoding such an enzyme (Thompson, J.S. and Malamy, M.H. (1990) J. Bacteriol. 172, 2584-2593) hybridized with DNA from the Cpm(R) mutants, their Cpm(s) parental strains as well as clinical Cpm(R) isolates, but not from randomly chosen carbapenem-susceptible strains. The possibility is considered that mutations leading to expression of the silent carbapenemase gene, and thereby to clinically relevant carbapenem resistance, may also occur in the clinical setting.