High specificity of cphA-encoded metallo-beta-lactamase from Aeromonas hydrophila AE036 for carbapenems and its contribution to beta-lactam resistance.
The Aeromonas hydrophila AE036 chromosome contains a cphA gene encoding a metallo-beta-lactamase highly active against carbapenem antibiotics. This enzyme was induced in strain AE036 to the same extent by both benzylpenicillin and imipenem. When the cphA gene was inserted into plasmid pACYC184, used to transform Escherichia coli DH5 alpha, the MICs of imipenem, meropenem, and penem HRE664 for recombinant clone DH5 alpha(pAA20R), expressing the Aeromonas metallo-beta-lactamase, were significantly increased, but those of penicillins and cephalosporins were not. When the metallo-beta-lactamase purified from E. coli DH5 alpha(pAA20R) was assayed with several beta-lactam substrates, it hydrolyzed carbapenems but not penicillins or cephalosporins efficiently. These results demonstrate that this metallo-beta-lactamase possesses an unusual spectrum of activity compared with all the other class B enzymes identified so far, being active on penems and carbapenems only. This enzyme may thus contribute to the development of resistance to penems and carbapenems but not other beta-lactams.
Segatore
B
B
Department of Biomedical Sciences and Technologies and of Biometrics, Faculty of Medicine, University of L'Aquila, Italy.
Massidda
O
O
Satta
G
G
Setacci
D
D
Amicosante
G
G
D016980:Aeromonas hydrophila / Q000201:enzymology* / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015780:Carbapenems / Q000378:metabolism* / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004492:Edetic Acid / Q000494:pharmacology; D004790:Enzyme Induction; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics*; D006868:Hydrolysis; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D004492:Edetic Acid; D001618:beta-Lactamases; C082063:cphA protein, Aeromonas hydrophila