Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim
{"title":"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。","authors":"Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim","doi":"10.1099/mic.0.001509","DOIUrl":null,"url":null,"abstract":"<p><p>Adherent-invasive <i>Escherichia coli</i> (AIEC) has been implicated in the aetiology of Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract. The presence of <i>Enterobacteriaceae</i>, 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 <i>envC</i> 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 <i>envC</i> gene exhibited impaired cell division. Furthermore, <i>envC</i> deletion led to a diminished outer membrane barrier, as seen in our finding that the <i>envC</i> mutant became susceptible to vancomycin. Finally, we found that the <i>envC</i> 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.</p>","PeriodicalId":49819,"journal":{"name":"Microbiology-Sgm","volume":"170 10","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570989/pdf/","citationCount":"0","resultStr":"{\"title\":\"Outer membrane barrier impairment by <i>envC</i> deletion reduces gut colonization of Crohn's disease pathobiont <i>Escherichia coli</i>.\",\"authors\":\"Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim\",\"doi\":\"10.1099/mic.0.001509\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Adherent-invasive <i>Escherichia coli</i> (AIEC) has been implicated in the aetiology of Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract. The presence of <i>Enterobacteriaceae</i>, 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 <i>envC</i> 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 <i>envC</i> gene exhibited impaired cell division. Furthermore, <i>envC</i> deletion led to a diminished outer membrane barrier, as seen in our finding that the <i>envC</i> mutant became susceptible to vancomycin. Finally, we found that the <i>envC</i> 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.</p>\",\"PeriodicalId\":49819,\"journal\":{\"name\":\"Microbiology-Sgm\",\"volume\":\"170 10\",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11570989/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbiology-Sgm\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1099/mic.0.001509\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiology-Sgm","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1099/mic.0.001509","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Outer membrane barrier impairment by envC deletion reduces gut colonization of Crohn's disease pathobiont Escherichia coli.
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.
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.