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oai:kagawa-u.repo.nii.ac.jp:00007449 2024-10-31T08:01:38Z 13:40

The human gut microbe Bacteroides thetaiotaomicron suppresses toxin release from Clostridium difficile by inhibiting autolysis 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 Elahi, Miad エラヒ, ミアド Elahi, Miad open access © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. No Embargo. Bacteroides thetaiotaomicron Clostridium difficile toxin autolysis cell wall 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. eng doctoral thesis P https://kagawa-u.repo.nii.ac.jp/records/7449 https://doi.org/10.3390/antibiotics10020187 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7918992/ 33671889 500001471038 甲第779号 博士（医学） 2021-06-29 16201 香川大学 Kagawa University https://kagawa-u.repo.nii.ac.jp/record/7449/files/Med_A779.pdf application/pdf 1.1 MB 2021-07-13 https://kagawa-u.repo.nii.ac.jp/record/7449/files/Med_A779_abstract.pdf application/pdf 49.5 kB 2021-07-13 https://kagawa-u.repo.nii.ac.jp/record/7449/files/Med_A779_result.pdf application/pdf 115.6 kB 2021-07-13