Outer membrane barrier impairment by envC deletion reduces gut colonization of Crohn's disease pathobiont Escherichia coli.

IF 2.6 4区 生物学 Q3 MICROBIOLOGY
Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim
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Abstract

Adherent-invasive Escherichia coli (AIEC) has been implicated in the aetiology of Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract. The presence of Enterobacteriaceae, including AIEC, is heightened in the intestines of CD patients. Therefore, inhibiting AIEC colonization in the gastrointestinal tract could be a promising therapeutic intervention for CD. This study aims to assess the potential of EnvC as a novel therapeutic target, examining how disrupting EnvC activity through the deletion of the envC gene decreases AIEC gut colonization levels. EnvC serves as a catalyst for peptidoglycan (also called murein) amidases, facilitating bacterial cell division. An AIEC mutant lacking the envC gene exhibited impaired cell division. Furthermore, envC deletion led to a diminished outer membrane barrier, as seen in our finding that the envC mutant became susceptible to vancomycin. Finally, we found that the envC mutant is impaired in competitive gut colonization in a dysbiotic mouse model. The colonization defects might be attributable to reduced resistance to colonic bile acids, as evidenced by our finding that increased colonic levels of bile acids inhibited the colonization of the gastrointestinal tract by AIEC strains. The present findings suggest that targeting bacterial cell division through the inhibition of EnvC activity could represent a promising intervention for CD.

envC缺失导致外膜屏障受损,从而减少了克罗恩病致病大肠杆菌的肠道定植。
粘附侵入性大肠埃希菌(AIEC)与克罗恩病(CD)的病因有关,克罗恩病是一种慢性胃肠道炎症性疾病。包括 AIEC 在内的肠杆菌科细菌在克罗恩病患者的肠道中大量存在。因此,抑制 AIEC 在胃肠道中的定植可能是一种很有前景的 CD 治疗干预措施。本研究旨在评估 EnvC 作为新型治疗靶点的潜力,研究如何通过删除 envC 基因来破坏 EnvC 的活性,从而降低 AIEC 的肠道定植水平。EnvC 是肽聚糖(又称金霉素)酰胺酶的催化剂,可促进细菌细胞分裂。缺乏 envC 基因的 AIEC 突变体表现出细胞分裂障碍。此外,envC 基因缺失会导致外膜屏障减弱,我们发现 envC 突变体对万古霉素易感。最后,我们发现 envC 突变体在菌群失调小鼠模型中的竞争性肠道定植能力受损。定植缺陷可能是由于对结肠胆汁酸的抵抗力降低所致,我们发现结肠胆汁酸水平的增加抑制了 AIEC 菌株在胃肠道的定植。本研究结果表明,通过抑制 EnvC 活性来靶向细菌细胞分裂可能是一种很有前景的 CD 干预方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Microbiology-Sgm
Microbiology-Sgm 生物-微生物学
CiteScore
4.60
自引率
7.10%
发文量
132
审稿时长
3.0 months
期刊介绍: We publish high-quality original research on bacteria, fungi, protists, archaea, algae, parasites and other microscopic life forms. Topics include but are not limited to: Antimicrobials and antimicrobial resistance Bacteriology and parasitology Biochemistry and biophysics Biofilms and biological systems Biotechnology and bioremediation Cell biology and signalling Chemical biology Cross-disciplinary work Ecology and environmental microbiology Food microbiology Genetics Host–microbe interactions Microbial methods and techniques Microscopy and imaging Omics, including genomics, proteomics and metabolomics Physiology and metabolism Systems biology and synthetic biology The microbiome.
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