Novel SHV-derived extended-spectrum beta-lactamase, SHV-57, that confers resistance to ceftazidime but not cefazolin.
A new SHV-derived extended-spectrum beta-lactamase, SHV-57, that confers high-level resistance to ceftazidime but not cefotaxime or cefazolin was identified from a national surveillance study conducted in Taiwan in 1998. An Escherichia coli isolate resistant to ampicillin, cephalothin, and ceftazidime but sensitive to cefoxitin, ceftriaxone, cefotaxime, imipenem, and a narrow-spectrum cephem (cefazolin) was isolated from the urine of a patient treated with beta-lactam antibiotics. Resistance to beta-lactams was conjugatively transferred with a plasmid of about 50 kbp. The pI of this enzyme was 8.3. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 861 bases (GenBank accession number AY223863). Kinetic parameters showed that SHV-57 had a poor affinity to cefazolin. The K(m) value toward cefazolin (5.57 x 10(3) muM) was extremely high in comparison to those toward ceftazidime (30.9 muM) and penicillin G (67 muM), indicating its low affinity to cefazolin. Although the K(m) value of the beta-lactamase inhibitor was too high for the study of catalytic activity (k(cat)), indicating the low k(cat) of SHV-57, the SHV-57 carrier was highly susceptible to a beta-lactam-beta-lactamase inhibitor combination. Comparison of the three-dimensional molecular model of SHV-57 with that of the SHV-1 beta-lactamase suggests that the substitution of arginine for leucine-169 in the Omega loop is important for the substrate specificity.
Ma
Ling
L
Division of Clinical Research, National Health Research Institutes (99), 128, Yen-Chiu-Yuan Rd., Sec. 2., Taipei, 11529, Taiwan.
Alba
Jimena
J
Chang
Feng-Yee
FY
Ishiguro
Masaji
M
Yamaguchi
Keizo
K
Siu
L K
LK
Ishii
Yoshikazu
Y
D002437:Cefazolin / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D003001:Cloning, Molecular; D003227:Conjugation, Genetic; D004269:DNA, Bacterial / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007525:Isoelectric Focusing; D007700:Kinetics; D008297:Male; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D013624:Taiwan; D001618:beta-Lactamases / Q000378:metabolism*
D002511:Cephalosporins; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D002442:Ceftazidime; C037106:endodeoxyribonuclease NdeI; C034510:CTCGAG-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D001618:beta-Lactamases; C498059:beta-lactamase SHV-57, E coli; D002437:Cefazolin