Dataset Information

Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A beta-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.

ABSTRACT: The sequence of the gene encoding a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-4) was determined. It was located in a plasmid harbored by a Salmonella typhimurium strain. CTX-M-4 was similar to the plasmidic cefotaxime-hydrolyzing beta-lactamases CTX-M-2 and Toho-1 and related to the chromosomal beta-lactamase of Klebsiella oxytoca. A Ser-237-->Ala substitution, introduced by site-directed mutagenesis, caused minor alterations in the interaction of CTX-M-4 with beta-lactams, reducing slightly the relative hydrolytic activity against cefotaxime and the susceptibility to inhibition by clavulanate.

SUBMITTER: Gazouli M

PROVIDER: S-EPMC105797 | biostudies-literature | 1998 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A beta-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.

Gazouli M M Tzelepi E E Sidorenko S V SV Tzouvelekis L S LS

Antimicrobial agents and chemotherapy 19980501 5

The sequence of the gene encoding a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-4) was determined. It was located in a plasmid harbored by a Salmonella typhimurium strain. CTX-M-4 was similar to the plasmidic cefotaxime-hydrolyzing beta-lactamases CTX-M-2 and Toho-1 and related to the chromosomal beta-lactamase of Klebsiella oxytoca. A Ser-237-->Ala substitution, introduced by site-directed mutagenesis, caused minor alterations in the interaction of CTX-M-4 with beta-lactams, reducing sli ...[more]

PMID: 9593162

Similar Datasets

Project description:Escherichia coli TUH12191, which is resistant to piperacillin, cefazolin, cefotiam, ceftizoxime, cefuzonam, and aztreonam but is susceptible to cefoxitin, latamoxef, flomoxef, and imipenem, was isolated from the urine of a patient treated with beta-lactam antibiotics. The beta-lactamase (Toho-1) purified from the bacteria had a pI of 7.8, had a molecular weight of about 29,000, and hydrolyzed beta-lactam antibiotics such as penicillin G, ampicillin, oxacillin, carbenicillin, piperacillin, cephalothin, cefoxitin, cefotaxime, ceftazidime, and aztreonam. Toho-1 was markedly inhibited by beta-lactamase inhibitors such as clavulanic acid and tazobactam. Resistance to beta-lactams, streptomycin, spectinomycin, sulfamethoxazole, and trimethoprim was transferred by conjugational transfer from E. coli TUH12191 to E. coli ML4903, and the transferred plasmid was about 58 kbp, belonging to incompatibility group M. The cefotaxime resistance gene for Toho-1 was subcloned from the 58-kbp plasmid by transformation of E. coli MV1184. The sequence of the gene for Toho-1 was determined, and the open reading frame of the gene consisted of 873 or 876 bases (initial sequence, ATGATG). The nucleotide sequence of the gene (DDBJ accession number D37830) was found to be about 73% homologous to the sequence of the gene encoding a class A beta-lactamase produced by Klebsiella oxytoca E23004. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 290 or 291 amino acid residues, which contained amino acid motifs common to class A beta-lactamases (70SXXK, 130SDN, and 234KTG). Toho-1 was about 83% homologous to the beta-lactamase mediated by the chromosome of K. oxytoca D488 and the beta-lactamase mediated by the plasmid of E. coli MEN-1. Therefore, the newly isolated beta-lactamase Toho-1 produced by E. coli TUH12191 is similar to beta-lactamases produced by K. oxytoca D488, K. oxytoca E23004, and E. coli MEN-1 rather than to mutants of TEM or SHV enzymes. Toho-1 has shown the highest degree of similarity to K. oxytoca class A beta-lactamase. Detailed comparison of Toho-1 with other beta-lactamases implied that replacement of Asn-276 by Arg with the concomitant substitution of Thr for Arg-244 is an important mutation in the extension of the substrate specificity.

Dataset Information

Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A beta-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.

Publications

Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A beta-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets