Page, Michael I. (2002) Understanding metallo β-lactamases. American Society for Microbiology News, 68 (5). pp. 217-221.
Restricted to Repository staff only
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.
|Additional Information:||© 2002 American Society for Microbiology|
|Uncontrolled Keywords:||metallo β-lactamases|
|Subjects:||Q Science > Q Science (General)|
Q Science > QD Chemistry
|Schools:||School of Applied Sciences|
School of Applied Sciences > Biomolecular Sciences Research Centre
Bounaga, S., A. P. Laws, M. Galleni, and M. I. Page. 1998. The mechanism of catalysis and the inhibition of Bacillus cereus zinc-dependent ß-lactamase Biochem. J. 331:703-711.
Bounaga, S., M. Galleni, A. P. Laws, and M. I. Page. 2001. Cysteinyl peptide inhibitors of B. cereus zinc ß-lactamase. Bioorg. Med. Chem. 9:503-510.
de Seny, D., C. Prosperi-Meys, C. Bebrone, G. M. Rossolini, M. I. Page, P. Noel, J.-M. Frere, and M. Galleni. Mutational analysis of the two zinc binding sites of the Bacillus cereus 569/J/9 metallo-ß-lactamase. Biochem. J., in press.
Page, M. I., and A. P. Laws. 1998. The mechanism of catalysis and the inhibition of ß-lactamases. Chem. Commun. 1998:1609-1617.
Paul-Soto, R, R. Bauer, J.-M. Frere, M. Galleni, W. Meyer-Klaucke, H. Nolting, G. M. Rossolini, D. de Seny, M. Hernandez-Valladares, M. Zeppezauer, and H.-W. Adolph. 1999. Mono- and binuclear Zn2+- ß-lactamase J. Biol. Chem. 274:13242-13249
|Depositing User:||Sara Taylor|
|Date Deposited:||11 Feb 2008 11:28|
|Last Modified:||28 Jul 2010 19:22|
Downloader CountriesMore statistics for this item...
Item control for Repository Staff only: