Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.

Salmonella enterica serovar Typhimurium (S. Tm) is a major cause of gastrointestinal diseases worldwide. To date, options for prevention or curative therapy remain limited. The gut microbiota plays a protective role against enteric diseases, particularly in preventing establishment and proliferation...

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Main Authors: Christopher Schubert, Jana Näf, Lisa Petukhov, Leanid Laganenka, Yassine Cherrak, Wolf-Dietrich Hardt
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-06-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1013232
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author Christopher Schubert
Jana Näf
Lisa Petukhov
Leanid Laganenka
Yassine Cherrak
Wolf-Dietrich Hardt
author_facet Christopher Schubert
Jana Näf
Lisa Petukhov
Leanid Laganenka
Yassine Cherrak
Wolf-Dietrich Hardt
author_sort Christopher Schubert
collection DOAJ
description Salmonella enterica serovar Typhimurium (S. Tm) is a major cause of gastrointestinal diseases worldwide. To date, options for prevention or curative therapy remain limited. The gut microbiota plays a protective role against enteric diseases, particularly in preventing establishment and proliferation of S. Tm. While most research has focused on microbiota-mediated pathogen exclusion during the later, inflammation-dominated stages of infection, little is known about how microbiota members mitigate S. Tm early gut colonization. To address this gap, we conducted 24 h in vivo competitive experiments using S. Tm and different commensal E. coli strains. We observed a significant reduction in pathogen load, which was strain-specific and particularly evident with E. coli 8178. To investigate the underlying molecular mechanisms, we performed an in vivo screen using a rationally designed S. Tm library-which includes a wide range of carbohydrate utilization mutants-both in the absence and presence of E. coli strains. Our findings revealed that E. coli 8178-mediated S. Tm competition was driven by the exploitation of galactose during the early stage of infection. Identifying galactose as a key metabolite in pathogen exclusion by gut microbiota members enhances our mechanistic understanding of microbiota-mediated protection and opens new avenues for developing microbiota- and dietary-based strategies to better control intestinal infections.
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language English
publishDate 2025-06-01
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spelling doaj-art-ef14b786abb047b6a07a4608084274d12025-08-20T02:36:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-06-01216e101323210.1371/journal.ppat.1013232Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.Christopher SchubertJana NäfLisa PetukhovLeanid LaganenkaYassine CherrakWolf-Dietrich HardtSalmonella enterica serovar Typhimurium (S. Tm) is a major cause of gastrointestinal diseases worldwide. To date, options for prevention or curative therapy remain limited. The gut microbiota plays a protective role against enteric diseases, particularly in preventing establishment and proliferation of S. Tm. While most research has focused on microbiota-mediated pathogen exclusion during the later, inflammation-dominated stages of infection, little is known about how microbiota members mitigate S. Tm early gut colonization. To address this gap, we conducted 24 h in vivo competitive experiments using S. Tm and different commensal E. coli strains. We observed a significant reduction in pathogen load, which was strain-specific and particularly evident with E. coli 8178. To investigate the underlying molecular mechanisms, we performed an in vivo screen using a rationally designed S. Tm library-which includes a wide range of carbohydrate utilization mutants-both in the absence and presence of E. coli strains. Our findings revealed that E. coli 8178-mediated S. Tm competition was driven by the exploitation of galactose during the early stage of infection. Identifying galactose as a key metabolite in pathogen exclusion by gut microbiota members enhances our mechanistic understanding of microbiota-mediated protection and opens new avenues for developing microbiota- and dietary-based strategies to better control intestinal infections.https://doi.org/10.1371/journal.ppat.1013232
spellingShingle Christopher Schubert
Jana Näf
Lisa Petukhov
Leanid Laganenka
Yassine Cherrak
Wolf-Dietrich Hardt
Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.
PLoS Pathogens
title Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.
title_full Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.
title_fullStr Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.
title_full_unstemmed Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.
title_short Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut.
title_sort strain specific galactose utilization by commensal e coli mitigates salmonella establishment in the gut
url https://doi.org/10.1371/journal.ppat.1013232
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