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Mechanisms of Resistance

Penicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in Japan

Satoshi Nakano, Takao Fujisawa, Yutaka Ito, Bin Chang, Yasufumi Matsumura, Masaki Yamamoto, Shigeru Suga, Makoto Ohnishi, Miki Nagao
Satoshi Nakano
Kyoto University Graduate School of Medicine, Kyoto, Japan
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Takao Fujisawa
National Hospital Organization Mie National Hospital, Tsu, Japan
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Yutaka Ito
Nagoya City University Graduate School of Medical Science, Nagoya, Japan
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Bin Chang
National Institute of Infectious Diseases, Tokyo, Japan
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Yasufumi Matsumura
Kyoto University Graduate School of Medicine, Kyoto, Japan
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Masaki Yamamoto
Kyoto University Graduate School of Medicine, Kyoto, Japan
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Shigeru Suga
National Hospital Organization Mie National Hospital, Tsu, Japan
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Makoto Ohnishi
National Institute of Infectious Diseases, Tokyo, Japan
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Miki Nagao
Kyoto University Graduate School of Medicine, Kyoto, Japan
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DOI: 10.1128/AAC.00711-19
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ABSTRACT

Since the introduction of pneumococcal conjugate vaccines, the prevalence of non-meropenem-susceptible pneumococci has been increasing in Japan. In an earlier study, we demonstrated that multidrug-resistant serotype 15A-ST63 in Japan has a specific pbp1a sequence (pbp1a-13) that could promote meropenem resistance. To trace the origin of pbp1a, we analyzed isolates of serotype 19A-CC3111, which is the most prevalent non-meropenem-susceptible clone in Japan. We analyzed a total of 119 serotype 19A-CC3111 strains recovered in Japan using whole-genome sequencing. Of the 119 isolates, 53 (44.5%) harbored pbp1a-13, indicating that the clone may be the primary reservoir of the pbp1a type and that the pbp1a region may be horizontally transferred between different serotype strains. The single acquisition of pbp1a-13 seemed to cause only penicillin resistance and not multidrug resistance; a combination of penicillin-binding protein (PBP) recombination in the pbp2b and/or pbp2x region(s) with acquisition of pbp1a-13 caused multidrug resistance. Conserved amino acid motif analysis suggested that the pbp1a 370SXXK, pbp2b 448SXN, and pbp2x 337SXXN motifs were the candidates for amino acid substitutions increasing the MICs of meropenem, cefotaxime, and penicillin. We identified a specific clone that was correlated with multidrug resistance, although no correlation was observed between phylogenetic trees generated using core genomes and those generated with only the cps locus. All tested isolates were highly erythromycin resistant, and most harbored mefE within macrolide efflux genetic assembly (MEGA) elements and ermB within Tn917, which was inserted within Tn916 and exhibited a structure identical to that of Tn2017.

FOOTNOTES

    • Received 6 April 2019.
    • Returned for modification 8 May 2019.
    • Accepted 15 June 2019.
    • Accepted manuscript posted online 24 June 2019.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.00711-19.

  • Copyright © 2019 American Society for Microbiology.

All Rights Reserved.

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Penicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in Japan
Satoshi Nakano, Takao Fujisawa, Yutaka Ito, Bin Chang, Yasufumi Matsumura, Masaki Yamamoto, Shigeru Suga, Makoto Ohnishi, Miki Nagao
Antimicrobial Agents and Chemotherapy Aug 2019, 63 (9) e00711-19; DOI: 10.1128/AAC.00711-19

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Penicillin-Binding Protein Typing, Antibiotic Resistance Gene Identification, and Molecular Phylogenetic Analysis of Meropenem-Resistant Streptococcus pneumoniae Serotype 19A-CC3111 Strains in Japan
Satoshi Nakano, Takao Fujisawa, Yutaka Ito, Bin Chang, Yasufumi Matsumura, Masaki Yamamoto, Shigeru Suga, Makoto Ohnishi, Miki Nagao
Antimicrobial Agents and Chemotherapy Aug 2019, 63 (9) e00711-19; DOI: 10.1128/AAC.00711-19
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KEYWORDS

19A
Japan
PBP typing
ST3111
Streptococcus pneumoniae
meropenem
multidrug resistance
PBP1a
pbp2b
PBP2x

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