Novel Cefotaximase (CTX-M-16) with Increased Catalytic Efficiency Due to Substitution Asp-240→Gly
AUTOR(ES)
Bonnet, R.
FONTE
American Society for Microbiology
RESUMO
Three clinical strains (Escherichia coli Rio-6, E. coli Rio-7, and Enterobacter cloacae Rio-9) collected in 1996 and 1999 from hospitals in Rio de Janeiro (Brazil) were resistant to broad-spectrum cephalosporins and gave a positive double-disk synergy test. Two blaCTX-M genes encoding β-lactamases of pl 7.9 and 8.2 were implicated in this resistance: the blaCTX-M-9 gene observed in E. coli Rio-7 and E. cloacae Rio-9 and a novel CTX-M-encoding gene, designated blaCTX-M-16, observed in E. coli strain Rio-6. The deduced amino acid sequence of CTX-M-16 differed from CTX-M-9 only by the substitution Asp-240→Gly. The CTX-M-16-producing E. coli transformant exhibited the same level of resistance to cefotaxime (MIC, 16 μg/ml) but had a higher MIC of ceftazidime (MIC, 8 versus 1 μg/ml) than the CTX-M-9-producing transformant. Enzymatic studies revealed that CTX-M-16 had a 13-fold higher affinity for aztreonam and a 7.5-fold higher kcat for ceftazidime than CTX-M-9, thereby showing that the residue in position 240 can modulate the enzymatic properties of CTX-M enzymes. The two blaCTX-M-9 genes and the blaCTX-M-16 gene were located on different plasmids, suggesting the presence of mobile elements associated with CTX-M-encoding genes. CTX-M-2 and CTX-M-8 enzymes were found in Brazil in 1996, and two other CTX-M β-lactamases, CTX-M-9 and CTX-M-16, were subsequently observed. These reports are evidence of the diversity of CTX-M-type extended-spectrum β-lactamases in Brazil.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=90641Documentos Relacionados
- High-Level Resistance to Ceftazidime Conferred by a Novel Enzyme, CTX-M-32, Derived from CTX-M-1 through a Single Asp240-Gly Substitution
- Effects of Ser130Gly and Asp240Lys Substitutions in Extended-Spectrum β-Lactamase CTX-M-9
- Molecular Characterization of a Novel Plasmid-Encoded Cefotaximase (CTX-M-12) Found in Clinical Klebsiella pneumoniae Isolates from Kenya
- A Novel CTX-M β-Lactamase (CTX-M-8) in Cefotaxime-Resistant Enterobacteriaceae Isolated in Brazil
- CTX-M-1, CTX-M-3, and CTX-M-14 β-Lactamases from Enterobacteriaceae Isolated in France