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

Wael Elhenawy, Sarah Hordienko, Steven Gould, Alexander M. Oberc, Caressa N. Tsai, Troy P. Hubbard, Matthew K. Waldor and Brian K. Coombes ()
Additional contact information
Wael Elhenawy: McMaster University
Sarah Hordienko: McMaster University
Steven Gould: McMaster University
Alexander M. Oberc: McMaster University
Caressa N. Tsai: McMaster University
Troy P. Hubbard: Division of Infectious Diseases, Brigham & Women’s Hospital
Matthew K. Waldor: Division of Infectious Diseases, Brigham & Women’s Hospital
Brian K. Coombes: McMaster University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-22306-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22306-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-22306-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().