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High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli
Adherent-invasive Escherichia coli (AIEC) are pathogenic bacteria frequently isolated from patients who have Crohn’s disease (CD). Despite the phenotypic differences between AIEC and commensal E. coli, comparative genomic approaches have been unable to differentiate these two groups, making the iden...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016931/ https://www.ncbi.nlm.nih.gov/pubmed/33795670 http://dx.doi.org/10.1038/s41467-021-22306-w |
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author | Elhenawy, Wael Hordienko, Sarah Gould, Steven Oberc, Alexander M. Tsai, Caressa N. Hubbard, Troy P. Waldor, Matthew K. Coombes, Brian K. |
author_facet | Elhenawy, Wael Hordienko, Sarah Gould, Steven Oberc, Alexander M. Tsai, Caressa N. Hubbard, Troy P. Waldor, Matthew K. Coombes, Brian K. |
author_sort | Elhenawy, Wael |
collection | PubMed |
description | Adherent-invasive Escherichia coli (AIEC) are pathogenic bacteria frequently isolated from patients who have Crohn’s disease (CD). Despite the phenotypic differences between AIEC and commensal E. coli, comparative genomic approaches have been unable to differentiate these two groups, making the identification of key virulence factors a challenge. Here, we conduct a high-resolution, in vivo genetic screen to map AIEC genes required for intestinal colonization of mice. In addition, we use in vivo RNA-sequencing to define the host-associated AIEC transcriptome. We identify diverse metabolic pathways required for efficient gut colonization by AIEC and show that a type IV secretion system (T4SS) is required to form biofilms on the surface of epithelial cells, thereby promoting AIEC persistence in the gut. E. coli isolated from CD patients are enriched for a T4SS, suggesting a possible connection to disease activity. Our findings establish the T4SS as a principal AIEC colonization factor and highlight the use of genome-wide screens in decoding the infection biology of CD-associated bacteria that otherwise lack a defined genetic signature. |
format | Online Article Text |
id | pubmed-8016931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80169312021-04-16 High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli Elhenawy, Wael Hordienko, Sarah Gould, Steven Oberc, Alexander M. Tsai, Caressa N. Hubbard, Troy P. Waldor, Matthew K. Coombes, Brian K. Nat Commun Article Adherent-invasive Escherichia coli (AIEC) are pathogenic bacteria frequently isolated from patients who have Crohn’s disease (CD). Despite the phenotypic differences between AIEC and commensal E. coli, comparative genomic approaches have been unable to differentiate these two groups, making the identification of key virulence factors a challenge. Here, we conduct a high-resolution, in vivo genetic screen to map AIEC genes required for intestinal colonization of mice. In addition, we use in vivo RNA-sequencing to define the host-associated AIEC transcriptome. We identify diverse metabolic pathways required for efficient gut colonization by AIEC and show that a type IV secretion system (T4SS) is required to form biofilms on the surface of epithelial cells, thereby promoting AIEC persistence in the gut. E. coli isolated from CD patients are enriched for a T4SS, suggesting a possible connection to disease activity. Our findings establish the T4SS as a principal AIEC colonization factor and highlight the use of genome-wide screens in decoding the infection biology of CD-associated bacteria that otherwise lack a defined genetic signature. Nature Publishing Group UK 2021-04-01 /pmc/articles/PMC8016931/ /pubmed/33795670 http://dx.doi.org/10.1038/s41467-021-22306-w Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Elhenawy, Wael Hordienko, Sarah Gould, Steven Oberc, Alexander M. Tsai, Caressa N. Hubbard, Troy P. Waldor, Matthew K. Coombes, Brian K. High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli |
title | High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli |
title_full | High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli |
title_fullStr | High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli |
title_full_unstemmed | High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli |
title_short | High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli |
title_sort | high-throughput fitness screening and transcriptomics identify a role for a type iv secretion system in the pathogenesis of crohn’s disease-associated escherichia coli |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016931/ https://www.ncbi.nlm.nih.gov/pubmed/33795670 http://dx.doi.org/10.1038/s41467-021-22306-w |
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