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Antimicrobial Agents and Chemotherapy, May 2001, p. 1343-1348, Vol. 45, No. 5
Department of Microbiology, School of
Medicine and Environmental Infectious Disease, Graduate School of
Medical Sciences, Kitasato University, Sagamihara, Kanagawa
228-8555,1 and Department of
Otolaryngology, Nagasaki University School of Medicine, Nagasaki
852-8501,2 Japan
Received 3 July 2000/Returned for modification 20 August
2000/Accepted 30 January 2001
In 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 blaIMP and
the genes for TEM-1-type
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.5.1343-1348.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Plasmid-Encoded Metallo-
-Lactamase (IMP-6)
Conferring Resistance to Carbapenems, Especially Meropenem
-lactamases as well as producing both types
of
-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-
-lactamase gene, and is obtained by PCR amplification of
pKU501. The sequence of the metallo-
-lactamase gene in pKU502 was
determined and revealed that this metallo-
-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 kcat/Km 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.
*
Corresponding author. Mailing address: Department of
Otolaryngology, Nagasaki University School of Medicine, Nagasaki
852-8501, Japan. Phone: 81-95-849-7350. Fax: 81-95-849-7352. E-mail:
d300042c{at}stcc.nagasaki-u.ac.jp.
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