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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

Carbapenem-Nonsusceptible Haemophilus influenzae with Penicillin-Binding Protein 3 Containing an Amino Acid Insertion

http://hdl.handle.net/2237/00029068
6b36bdbf-88bc-49b0-a704-83adfd1716a5
名前 / ファイル ライセンス アクション
KItaokaAAC.pdf KItaokaAAC (1.0 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-11-14
タイトル
タイトル Carbapenem-Nonsusceptible Haemophilus influenzae with Penicillin-Binding Protein 3 Containing an Amino Acid Insertion
著者 Kitaoka, Kazuki

× Kitaoka, Kazuki

WEKO 87966

Kitaoka, Kazuki

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Kimura, Kouji

× Kimura, Kouji

WEKO 87967

Kimura, Kouji

Search repository
Kitanaka, Hiromitsu

× Kitanaka, Hiromitsu

WEKO 87968

Kitanaka, Hiromitsu

Search repository
Banno, Hirotsugu

× Banno, Hirotsugu

WEKO 87969

Banno, Hirotsugu

Search repository
Jin, Wanchun

× Jin, Wanchun

WEKO 87970

Jin, Wanchun

Search repository
Wachino, Jun-ichi

× Wachino, Jun-ichi

WEKO 87971

Wachino, Jun-ichi

Search repository
Arakawa, Yoshichika

× Arakawa, Yoshichika

WEKO 87972

Arakawa, Yoshichika

Search repository
キーワード
主題Scheme Other
主題 Haemophilus influenzae
キーワード
主題Scheme Other
主題 carbapenems
キーワード
主題Scheme Other
主題 penicillin-binding proteins
抄録
内容記述 The prevalence of β-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae has become a clinical concern. In BLNAR isolates, amino acid substitutions in penicillin-binding protein 3 (PBP3) are relevant to the β-lactam resistance. Carbapenem-nonsusceptible H. influenzae isolates have been rarely reported. Through antimicrobial susceptibility testing, nucleotide sequence analysis of ftsI, encoding PBP3, and the utilization of a collection of H. influenzae clinical isolates in our laboratory, we obtained a carbapenem-nonsusceptible clinical isolate (NUBL1772) that possesses an altered PBP3 containing V525_N526insM. The aim of this study was to reveal the effect of altered PBP3 containing V525_N526insM on reduced carbapenem susceptibility. After generating recombinant strains with altered ftsI, we performed antimicrobial susceptibility testing and competitive binding assays with fluorescent penicillin (Bocillin FL) and carbapenems. Elevated carbapenem MICs were found for the recombinant strain harboring the entire ftsI gene of NUBL1772. The recombinant PBP3 of NUBL1772 also exhibited reduced binding to carbapenems. These results demonstrate that altered PBP3 containing V525_N526insM influences the reduced carbapenem susceptibility. The revertant mutant lacking the V525_N526insM exhibited lower MICs for carbapenems than NUBL1772, suggesting that this insertion affects reduced carbapenem susceptibility. The MICs of β-lactams for NUBL1772 were higher than those for the recombinant possessing ftsI of NUBL1772. NUBL1772 harbored AcrR with early termination, resulting in low-level transcription of acrB and high efflux pump activity. These findings suggest that the disruption of AcrR also contributes to the reduced carbapenem susceptibility found in NUBL1772. Our results provide the first evidence that the altered PBP3 containing V525_N526insM is responsible for the reduced susceptibility to carbapenems in H. influenzae.
内容記述タイプ Abstract
内容記述
内容記述 ファイル公開:2019/02/01
内容記述タイプ Other
出版者
出版者 American Society for Microbiology
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
DOI
関連識別子
識別子タイプ DOI
関連識別子 https://doi.org/10.1128/AAC.00671-18
ISSN(print)
収録物識別子タイプ ISSN
収録物識別子 0066-4804
ISSN(Online)
収録物識別子タイプ ISSN
収録物識別子 1098-6596
書誌情報 Antimicrobial Agents and Chemotherapy

巻 62, 号 8, p. e00671-18, 発行日 2018-08
著者版フラグ
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