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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.

ABSTRACT: 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.

SUBMITTER: Elhenawy W

PROVIDER: S-EPMC8016931 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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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.

Elhenawy Wael W Hordienko Sarah S Gould Steven S Oberc Alexander M AM Tsai Caressa N CN Hubbard Troy P TP Waldor Matthew K MK Coombes Brian K BK

Nature communications 20210401 1

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 ...[more]

PMID: 33795670

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Dataset Information

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.

Publications

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.

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