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.

Restricted to Repository staff only

Download (1MB)
Add to AnyAdd to TwitterAdd to FacebookAdd to LinkedinAdd to PinterestAdd to Email