التفاصيل البيبلوغرافية
| العنوان: |
Enterotoxigenic Escherichia coli degrades the host MUC2 mucin barrier to facilitate critical pathogen-enterocyte interactions in human small intestine |
| المؤلفون: |
Sheikh, Alaullah, Wangdi, Tamding, Vickers, Tim J, Aaron, Bailey, Palmer, Margot, Miller, Mark J, Kim, Seonyoung, Herring, Cassandra, Simoes, Rita, Crainic, Jennifer A, Gildersleeve, Jeffrey C, van der Post, Sjoerd, Hansson, Gunnar C, Fleckenstein, James M |
| المصدر: |
Open Access Publications |
| بيانات النشر: |
Digital Commons@Becker |
| سنة النشر: |
2022 |
| المجموعة: |
Washington University School of Medicine: Digital Commons@Becker |
| مصطلحات موضوعية: |
Bacterial Toxins, Diarrhea, Enterocytes, Enterotoxigenic Escherichia coli, Enterotoxins, Escherichia coli Infections, Escherichia coli Proteins, Humans, Intestine, Small, Mucin-2, Mucins |
| الوصف: |
Enterotoxigenic Escherichia coli (ETEC) isolates are genetically diverse pathological variants of E. coli defined by the production of heat-labile (LT) and/or heat-stable (ST) toxins. ETEC strains are estimated to cause hundreds of millions of cases of diarrheal illness annually. However, it is not clear that all strains are equally equipped to cause disease, and asymptomatic colonization with ETEC is common in low- to middle-income regions lacking basic sanitation and clean water where ETEC are ubiquitous. Recent molecular epidemiology studies have revealed a significant association between strains that produce EatA, a secreted autotransporter protein, and the development of symptomatic infection. Here, we demonstrate that LT stimulates production of MUC2 mucin by goblet cells in human small intestine, enhancing the protective barrier between pathogens and enterocytes. In contrast, using explants of human small intestine as well as small intestinal enteroids, we show that EatA counters this host defense by engaging and degrading the MUC2 mucin barrier to promote bacterial access to target enterocytes and ultimately toxin delivery, suggesting that EatA plays a crucial role in the molecular pathogenesis of ETEC. These findings may inform novel approaches to prevention of acute diarrheal illness as well as the sequelae associated with ETEC and other pathogens that rely on EatA and similar proteases for efficient interaction with their human hosts. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
https://digitalcommons.wustl.edu/open_access_pubs/11928Test; https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/viewcontent/EnterotoxigenicEscherichiaColiDegradesTheHostMUC2.pdfTest; https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/0/type/additional/viewcontent/Supplemental_material_0001.pdfTest; https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/1/type/additional/viewcontent/Supplemental_material_0002.xlsxTest; https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/2/type/additional/viewcontent/Supplemental_material_0003.xlsxTest; https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/3/type/additional/viewcontent/Supplemental_material_0004.movTest; https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/4/type/additional/viewcontent/Supplemental_material_0005.movTest |
| DOI: |
10.1128/IAI.00572-21 |
| الإتاحة: |
https://doi.org/10.1128/IAI.00572-21Test
https://digitalcommons.wustl.edu/open_access_pubs/11928Test
https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/viewcontent/EnterotoxigenicEscherichiaColiDegradesTheHostMUC2.pdfTest
https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/0/type/additional/viewcontent/Supplemental_material_0001.pdfTest
https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/1/type/additional/viewcontent/Supplemental_material_0002.xlsxTest
https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/2/type/additional/viewcontent/Supplemental_material_0003.xlsxTest
https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/3/type/additional/viewcontent/Supplemental_material_0004.movTest
https://digitalcommons.wustl.edu/context/open_access_pubs/article/12912/filename/4/type/additional/viewcontent/Supplemental_material_0005.movTest |
| رقم الانضمام: |
edsbas.B3558DC |
| قاعدة البيانات: |
BASE |
