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pubmed-article:11302793pubmed:abstractTextIn 1996, Serratia marcescens KU3838 was isolated from the urine of a patient with a urinary tract infection at a hospital in northern Japan and was found to contain the plasmid pKU501. Previously, we determined that pKU501 carries bla(IMP) and the genes for TEM-1-type beta-lactamases as well as producing both types of beta-lactamases (H. Yano, A. Kuga, K. Irinoda, R. Okamoto, T. Kobayashi, and M. Inoue, J. Antibiot. 52:1135-1139, 1999). pKU502 is a recombinant plasmid that contains a 1.5-kb DNA fragment, including the metallo-beta-lactamase gene, and is obtained by PCR amplification of pKU501. The sequence of the metallo-beta-lactamase gene in pKU502 was determined and revealed that this metallo-beta-lactamase gene differed from the gene encoding IMP-1 by one point mutation, leading to one amino acid substitution: 640-A in the base sequence of the IMP-1 gene was replaced by G, and Ser-196 was replaced by Gly in the mature enzyme. This enzyme was designated IMP-6. The strains that produced IMP-6 were resistant to carbapenems. The MICs of panipenem and especially meropenem were higher than the MIC of imipenem for these strains. The k(cat)/K(m) value of IMP-6 was about sevenfold higher against meropenem than against imipenem, although the MIC of meropenem for KU1917, which produced IMP-1, was lower than that of imipenem, and the MIC of panipenem was equal to that of imipenem. These results support the hypothesis that IMP-6 has extended substrate profiles against carbapenems. However, the activity of IMP-6 was very low against penicillin G and piperacillin. These results suggest that IMP-6 acquired high activity against carbapenems, especially meropenem, via the point mutation but in the process lost activity against penicillins. Although IMP-6 has reduced activity against penicillins due to this point mutation, pKU501 confers resistance to a variety of antimicrobial agents because it also produces TEM-1-type enzyme.lld:pubmed
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pubmed-article:11302793pubmed:authorpubmed-author:KobayashiTTlld:pubmed
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pubmed-article:11302793pubmed:articleTitlePlasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem.lld:pubmed
pubmed-article:11302793pubmed:affiliationDepartment of Microbiology, School of Medicine and Environmental Infectious Disease, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa 228-8555, Japan. d300042c@stcc.nagasaki-u.ac.jplld:pubmed
pubmed-article:11302793pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11302793pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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