Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A beta-lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.
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.
Gazouli
M
M
Department of Bacteriology, Hellenic Pasteur Institute, Athens, Greece.
Tzelepi
E
E
Sidorenko
S V
SV
Tzouvelekis
L S
LS
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001483:Base Sequence; D002439:Cefotaxime / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism*; D005798:Genes, Bacterial / Q000235:genetics*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics; D012694:Serine / Q000737:chemistry; D018440:beta-Lactam Resistance / Q000235:genetics; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D002511:Cephalosporins; D012694:Serine; C112790:CTX-M-4 protein, Salmonella typhimurium; D001618:beta-Lactamases; D002439:Cefotaxime