Commensal E. coli limits Salmonella gut invasion during inflammation by producing toxin-bound siderophores in a tonB-dependent manner.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2003]-

Escherichia coli*/metabolism ; Escherichia coli*/genetics ; Siderophores*/metabolism ; Salmonella typhimurium*/pathogenicity ; Salmonella typhimurium*/metabolism ; Inflammation*/metabolism ; Inflammation*/microbiology; Animals ; Mice ; Mice, Inbred C57BL ; Bacteriocins/metabolism ; Bacteriocins/pharmacology ; Gastrointestinal Microbiome ; Escherichia coli Proteins/metabolism ; Escherichia coli Proteins/genetics ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; Salmonella Infections/microbiology ; Salmonella Infections/metabolism ; Female ; Iron/metabolism ; Symbiosis ; Gastrointestinal Tract/microbiology ; Gastrointestinal Tract/metabolism

The gastrointestinal tract is densely colonized by a polymicrobial community known as the microbiota which serves as primary line of defence against pathogen invasion. The microbiota can limit gut-luminal pathogen growth at different stages of infection. This can be traced to specific commensal strains exhibiting direct or indirect protective functions. Although these mechanisms hold the potential to develop new approaches to combat enteric pathogens, they remain far from being completely described. In this study, we investigated how a mouse commensal Escherichia coli can outcompete Salmonella enterica serovar Typhimurium (S. Tm). Using a salmonellosis mouse model, we found that the commensal E. coli 8178 strain relies on a trojan horse trap strategy to limit S. Tm expansion in the inflamed gut. Combining mutants and reporter tools, we demonstrated that inflammation triggers the expression of the E. coli 8178 antimicrobial microcin H47 toxin which, when fused to salmochelin siderophores, can specifically alter S. Tm growth. This protective function was compromised upon disruption of the E. coli 8178 tonB-dependent catecholate siderophore uptake system, highlighting a previously unappreciated crosstalk between iron intake and microcin H47 activity. By identifying the genetic determinants mediating S. Tm competition, our work not only provides a better mechanistic understanding of the protective function displayed by members of the gut microbiota but also further expands the general contribution of microcins in bacterial antagonistic relationships. Ultimately, such insights can open new avenues for developing microbiota-based approaches to better control intestinal infections.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Cherrak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (Siderophores)
0 (Bacteriocins)
1403-96-9 (microcin)
0 (Escherichia coli Proteins)
0 (Membrane Proteins)
E1UOL152H7 (Iron)

Date Created: 20240612 Date Completed: 20240612 Latest Revision: 20240625

20240625

PMC11168627

10.1371/journal.pbio.3002616

38865418