The human gut microbe Bacteroides thetaiotaomicron suppresses toxin release from Clostridium difficile by inhibiting autolysis

Persistent ID (NDL): info:ndljp/pid/11711542

Material type: 博士論文

Author: Elahi, Miad

Publisher: -

Publication date: 2021-06-29

Material Format: Digital

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Name of awarding university/degree: 香川大学,博士（医学）

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Note (General)：: Disruption of the human gut microbiota by antibiotics can lead to Clostridium difficile (CD)-associated diarrhea. CD overgrowth and elevated CD toxins...

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Material Type: 博士論文
Title: The human gut microbe Bacteroides thetaiotaomicron suppresses toxin release from Clostridium difficile by inhibiting autolysis
Author/Editor: Elahi, Miad
Author Heading: Elahi, Miad
Publication Date: 2021-06-29
Publication Date (W3CDTF): 2021-06-29
Alternative Title: ヒト腸管内常在菌であるBacteroides thetaiotaomicron は Clostridium difficileの自己溶菌を抑制し、毒素産生を阻害する
Degree grantor/type: 香川大学
Date Granted: 2021-06-29
Date Granted (W3CDTF): 2021-06-29
Dissertation Number: 甲第779号
Degree Type: 博士（医学）
Conferring No. (Dissertation): 甲第779号
Text Language Code: eng
Alias of Author: Elahi, Miad
Subject Heading: Bacteroides thetaiotaomicron
Clostridium difficile
toxin
autolysis
cell wall
Target Audience: 一般
Note (General): Disruption of the human gut microbiota by antibiotics can lead to Clostridium difficile (CD)-associated diarrhea. CD overgrowth and elevated CD toxins result in gut inflammation. Herein, we report that a gut symbiont, Bacteroides thetaiotaomicron (BT), suppressed CD toxin production. The suppressive components are present in BT culture supernatant and are both heat- and proteinase K-resistant. Transposon-based mutagenesis indicated that the polysaccharide metabolism of BT is involved in the inhibitory effect. Among the genes identified, we focus on the methylerythritol 4-phosphate pathway gene gcpE, which supplies the isoprenoid backbone to produce the undecaprenyl phosphate lipid carrier that transports oligosaccharides across the membrane. Polysaccharide fractions prepared from the BT culture suppressed CD toxin production in vitro; the inhibitory effect of polysaccharide fractions was reduced in the gcpE mutant (ΔgcpE). The inhibitory effect of BT-derived polysaccharide fraction was abrogated by lysozyme treatment, indicating that cellwall-associated glycans are attributable to the inhibitory effect. BT-derived polysaccharide fraction did not affect CD toxin gene expression or intracellular toxin levels. An autolysis assay showed that CD cell autolysis was suppressed by BT-derived polysaccharide fraction, but the effect was reduced with that of ΔgcpE. These results indicate that cell wall-associated glycans of BT suppress CD toxin release by inhibiting cell autolysis.
DOI: info:doi/10.3390/antibiotics10020187
https://doi.org/info:doi/10.3390/antibiotics10020187
Persistent ID (NDL): info:ndljp/pid/11711542
https://dl.ndl.go.jp/pid/11711542
Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
https://dl.ndl.go.jp/collections/A00014
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2021-08-09T17:15:52+09:00
Date Created (W3CDTF): 2021-07-13
Format (IMT): PDF
Access Restrictions: 国立国会図書館内限定公開
Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
Availability of remote photoduplication service: 可
Periodical Title (URI): https://kagawa-u.repo.nii.ac.jp/records/7449
Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション
https://dl.ndl.go.jp