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Mechanisms of Resistance

SMB-1, a Novel Subclass B3 Metallo-β-Lactamase, Associated with ISCR1 and a Class 1 Integron, from a Carbapenem-Resistant Serratia marcescens Clinical Isolate

Jun-ichi Wachino, Hiroyuki Yoshida, Kunikazu Yamane, Satowa Suzuki, Mari Matsui, Takuya Yamagishi, Atsuko Tsutsui, Toshifumi Konda, Keigo Shibayama, Yoshichika Arakawa
Jun-ichi Wachino
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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  • For correspondence: wachino@nih.go.jp
Hiroyuki Yoshida
2Department of Infection Control and Prevention, Kobe University Hospital, 7-5-2 Chuo-ku, Kobe, Hyogo 650-0017, Japan
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Kunikazu Yamane
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
3Department of Public Health, Kawasaki Medical University, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
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Satowa Suzuki
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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Mari Matsui
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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Takuya Yamagishi
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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Atsuko Tsutsui
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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Toshifumi Konda
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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Keigo Shibayama
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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Yoshichika Arakawa
1Department of Bacteriology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
4Department of Bacteriology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
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DOI: 10.1128/AAC.05045-11
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ABSTRACT

A carbapenem-resistant Serratia marcescens strain, 10mdr148, was identified in a Japanese hospital in 2010. The carbapenem resistance of this strain was attributed to the production of a novel metallo-β-lactamase (MBL), named SMB-1 (Serratia metallo-β-lactamase). SMB-1 possessed a zinc binding motif, H(Q)XHXDH (residues 116 to 121), H196, and H263 and was categorized as a member of subclass B3 MBL. SMB-1 has 75% amino acid identity with the most closely related MBL, AMO1, of uncultured bacterium, recently identified through the metagenomic analysis of apple orchard soil. The introduction of blaSMB-1 into Escherichia coli conferred resistance to a variety of β-lactam antibiotics, penicillins, cephalosporins, and carbapenems, but not aztreonam, a resistance pattern consistent with those of other MBLs. SMB-1 demonstrated high kcat values of >500 s−1 for carbapenems, resulting in the highest hydrolyzing efficiency (kcat/Km) among the agents tested. The hydrolyzing activity of SMB-1 was well inhibited by chelating agents. The blaSMB-1 gene was located on the chromosome of S. marcescens strain 10mdr148 and at the 3′ end of the ISCR1 element in complex with a typical class 1 integron carrying aac(6′)-Ib and catB3 gene cassettes. Downstream of blaSMB-1, the second copy of the 3′conserved segment and ISCR1 were found. To our knowledge, this is the first subclass B3 MBL gene associated with an ISCR1 element identified in an Enterobacteriaceae clinical isolate. A variety of antibiotic resistance genes embedded with ISCR1 have been widely spread among Enterobacteriaceae clinical isolates, thus the further dissemination of blaSMB-1 mediated by ISCR1 transposition activity may become a future concern.

  • Copyright © 2011, American Society for Microbiology. All Rights Reserved.
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SMB-1, a Novel Subclass B3 Metallo-β-Lactamase, Associated with ISCR1 and a Class 1 Integron, from a Carbapenem-Resistant Serratia marcescens Clinical Isolate
Jun-ichi Wachino, Hiroyuki Yoshida, Kunikazu Yamane, Satowa Suzuki, Mari Matsui, Takuya Yamagishi, Atsuko Tsutsui, Toshifumi Konda, Keigo Shibayama, Yoshichika Arakawa
Antimicrobial Agents and Chemotherapy Oct 2011, 55 (11) 5143-5149; DOI: 10.1128/AAC.05045-11

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SMB-1, a Novel Subclass B3 Metallo-β-Lactamase, Associated with ISCR1 and a Class 1 Integron, from a Carbapenem-Resistant Serratia marcescens Clinical Isolate
Jun-ichi Wachino, Hiroyuki Yoshida, Kunikazu Yamane, Satowa Suzuki, Mari Matsui, Takuya Yamagishi, Atsuko Tsutsui, Toshifumi Konda, Keigo Shibayama, Yoshichika Arakawa
Antimicrobial Agents and Chemotherapy Oct 2011, 55 (11) 5143-5149; DOI: 10.1128/AAC.05045-11
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