Association of Amino Acid Substitutions in Penicillin-Binding Protein 3 with β-Lactam Resistance in β-Lactamase-Negative Ampicillin-Resistant <i>Haemophilus influenzae</i>
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- Kimiko Ubukata
- <!--label omitted: 1-->Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morookacho, Kohoku-ku, Yokohama,1
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- Yumi Shibasaki
- <!--label omitted: 1-->Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morookacho, Kohoku-ku, Yokohama,1
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- Kentarou Yamamoto
- <!--label omitted: 1-->Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morookacho, Kohoku-ku, Yokohama,1
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- Naoko Chiba
- <!--label omitted: 1-->Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morookacho, Kohoku-ku, Yokohama,1
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- Keiko Hasegawa
- <!--label omitted: 1-->Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morookacho, Kohoku-ku, Yokohama,1
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- Yasuo Takeuchi
- <!--label omitted: 1-->Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morookacho, Kohoku-ku, Yokohama,1
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- Keisuke Sunakawa
- <!--label omitted: 3-->Department of Infectious Diseases3 and
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- Matsuhisa Inoue
- <!--label omitted: 4-->Department of Bacteriology,4 School of Medicine, Kitasato University, Kitasato, Sagamihara, Japan
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- Masatoshi Konno
- <!--label omitted: 5-->Teikyo University School of Medicine,5Tokyo, and
抄録
<jats:title>ABSTRACT</jats:title> <jats:p> The affinity of [ <jats:sup>3</jats:sup> H]benzylpenicillin for penicillin-binding protein (PBP) 3A was reduced in 25 clinical isolates of β-lactamase-negative ampicillin (AMP)-resistant (BLNAR) <jats:italic>Haemophilus influenzae</jats:italic> for which the AMP MIC was ≥1.0 μg/ml. The affinities of PBP 3B and PBP 4 were also reduced in some strains. The sequences of the <jats:italic>ftsI</jats:italic> gene encoding the transpeptidase domain of PBP 3A and/or PBP 3B and of the <jats:italic>dacB</jats:italic> gene encoding PBP 4 were determined for these strains and compared to those of AMP-susceptible Rd strains. The BLNAR strains were classified into three groups on the basis of deduced amino acid substitutions in the <jats:italic>ftsI</jats:italic> gene, which is thought to be involved in septal peptidoglycan synthesis. His-517, near the conserved Lys-Thr-Gly (KTG) motif, was substituted for Arg-517 in group I strains ( <jats:italic>n</jats:italic> = 9), and Lys-526 was substituted for Asn-526 in group II strains ( <jats:italic>n</jats:italic> = 12). In group III strains ( <jats:italic>n</jats:italic> = 4), three residues (Met-377, Ser-385, and Leu-389), positioned near the conserved Ser-Ser-Asn (SSN) motif, were replaced with Ile, Thr, and Phe, respectively, in addition to the replacement with Lys-526. The MICs of cephem antibiotics with relatively high affinities for PBP 3A and PBP 3B were higher than those of AMP and meropenem for group III strains. The MICs of β-lactams for <jats:italic>H. influenzae</jats:italic> transformants into which the <jats:italic>ftsI</jats:italic> gene from BLNAR strains was introduced were as high as those for the donors, and PBP 3A and PBP 3B showed decreased affinities for β-lactams. There was no clear relationship between 7-bp deletions in the <jats:italic>dacB</jats:italic> gene and AMP susceptibility. Even though mutations in another gene(s) may be involved in β-lactam resistance, these data indicate that mutations in the <jats:italic>ftsI</jats:italic> gene are the most important for development of resistance to β-lactams in BLNAR strains. </jats:p>
収録刊行物
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- Antimicrobial Agents and Chemotherapy
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Antimicrobial Agents and Chemotherapy 45 (6), 1693-1699, 2001-06
American Society for Microbiology
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詳細情報 詳細情報について
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- CRID
- 1360574095454701312
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- NII論文ID
- 80012320923
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- ISSN
- 10986596
- 00664804
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