Page, Michael I. (2002) Understanding metallo β-lactamases. American Society for Microbiology News, 68 (5). pp. 217-221.

The ability to produce ß-lactamase enzymes is the major cause of the resistance of bacteria to ß-lactam antibiotics. These enzymes catalyze hydrolysis of four-membered ß-lactam rings, converting them into ß-amino acids that, unlike active members within this class of antibiotics, no longer interfere with bacterial cell synthesis and growth. The ß-lactamase enzymes are divided mechanistically into two groups, with those in classes A and C using serine as an active site residue, and those in class B using a metal ion, which is invariably zinc.

The class B metallo ß-lactamases were discovered more that 40 years ago by E. P. Abraham at the University of Oxford in a strain of Bacillus cereus that also produces two serine ß-lactamases. By 1985 researchers knew of two metallo ß-lactamases, whereas currently about 20 different strains, most of them human pathogens, are recognized as carrying such ß-lactamases. The genes encoding these enzymes generally are chromosomal but some are on plasmids, which enables them to spread among microorganisms more readily and thus makes them a greater cause of public health concern.

The metallo ß-lactamases are broad-spectrum enzymes that very effectively catalyze the hydrolysis of not only penicillins and cephalosporins but also other ß-lactam antibiotics, making pathogens that carry these enzymes a real problem in the clinic. In particular, they catalyze the hydrolysis of carbapenems, such as imipenem, that are generally resistant to serine ß-lactamases. Indeed, when these antibiotics were introduced, no known ß-lactamases catalyzed their hydrolysis. Currently, although several compounds effectively inhibit these metallo enzymes in vitro, none is clinically useful.

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