Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota

Bärbel Stecher, Riccardo Robbiani, Alan W Walker, Astrid M Westendorf, Manja Barthel, Marcus Kremer, Samuel Chaffron, Andrew J Macpherson, Jan Buer, Julian Parkhill, Gordon Dougan, Christian von Mering, Wolf-Dietrich Hardt

Research output: Contribution to journalArticle

597 Citations (Scopus)
3 Downloads (Pure)

Abstract

Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.
Original languageEnglish
Article numbere244
Number of pages13
JournalPLoS Biology
Volume5
Issue number10
DOIs
Publication statusPublished - 28 Aug 2007

Fingerprint

Salmonella
Salmonella enterica
Microbiota
Pathogens
intestinal microorganisms
Salmonella Typhimurium
inflammation
Inflammation
Bacteria
serotypes
colitis
Colitis
Interleukin-10
pathogens
Defects
inflammatory bowel disease
bacteria
mice
Chemical analysis
Coinfection

Keywords

  • animals
  • bacteria
  • colitis
  • female
  • genotype
  • in situ hybridization, fluorescence
  • intestines
  • male
  • mice
  • mice, inbred C3H,
  • mice, inbred C57BL
  • mice, inbred strains
  • microscopy, fluorescence
  • models, animal
  • molecular sequence data
  • mutation
  • phylogeny
  • RNA, ribosomal, 16S
  • Salmonella infections
  • Salmonella typhimurium
  • sequence analysis, DNA

Cite this

Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. / Stecher, Bärbel; Robbiani, Riccardo; Walker, Alan W; Westendorf, Astrid M; Barthel, Manja; Kremer, Marcus; Chaffron, Samuel; Macpherson, Andrew J; Buer, Jan; Parkhill, Julian; Dougan, Gordon; von Mering, Christian; Hardt, Wolf-Dietrich.

In: PLoS Biology, Vol. 5, No. 10, e244, 28.08.2007.

Research output: Contribution to journalArticle

Stecher, B, Robbiani, R, Walker, AW, Westendorf, AM, Barthel, M, Kremer, M, Chaffron, S, Macpherson, AJ, Buer, J, Parkhill, J, Dougan, G, von Mering, C & Hardt, W-D 2007, 'Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota', PLoS Biology, vol. 5, no. 10, e244. https://doi.org/10.1371/journal.pbio.0050244
Stecher, Bärbel ; Robbiani, Riccardo ; Walker, Alan W ; Westendorf, Astrid M ; Barthel, Manja ; Kremer, Marcus ; Chaffron, Samuel ; Macpherson, Andrew J ; Buer, Jan ; Parkhill, Julian ; Dougan, Gordon ; von Mering, Christian ; Hardt, Wolf-Dietrich. / Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. In: PLoS Biology. 2007 ; Vol. 5, No. 10.
@article{0ee248fdb5834556807630fa90df9832,
title = "Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota",
abstract = "Most mucosal surfaces of the mammalian body are colonized by microbial communities ({"}microbiota{"}). A high density of commensal microbiota inhabits the intestine and shields from infection ({"}colonization resistance{"}). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.",
keywords = "animals, bacteria, colitis, female, genotype, in situ hybridization, fluorescence, intestines, male, mice, mice, inbred C3H, , mice, inbred C57BL, mice, inbred strains, microscopy, fluorescence, models, animal, molecular sequence data, mutation, phylogeny, RNA, ribosomal, 16S, Salmonella infections, Salmonella typhimurium, sequence analysis, DNA",
author = "B{\"a}rbel Stecher and Riccardo Robbiani and Walker, {Alan W} and Westendorf, {Astrid M} and Manja Barthel and Marcus Kremer and Samuel Chaffron and Macpherson, {Andrew J} and Jan Buer and Julian Parkhill and Gordon Dougan and {von Mering}, Christian and Wolf-Dietrich Hardt",
year = "2007",
month = "8",
day = "28",
doi = "10.1371/journal.pbio.0050244",
language = "English",
volume = "5",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota

AU - Stecher, Bärbel

AU - Robbiani, Riccardo

AU - Walker, Alan W

AU - Westendorf, Astrid M

AU - Barthel, Manja

AU - Kremer, Marcus

AU - Chaffron, Samuel

AU - Macpherson, Andrew J

AU - Buer, Jan

AU - Parkhill, Julian

AU - Dougan, Gordon

AU - von Mering, Christian

AU - Hardt, Wolf-Dietrich

PY - 2007/8/28

Y1 - 2007/8/28

N2 - Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.

AB - Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.

KW - animals

KW - bacteria

KW - colitis

KW - female

KW - genotype

KW - in situ hybridization, fluorescence

KW - intestines

KW - male

KW - mice

KW - mice, inbred C3H,

KW - mice, inbred C57BL

KW - mice, inbred strains

KW - microscopy, fluorescence

KW - models, animal

KW - molecular sequence data

KW - mutation

KW - phylogeny

KW - RNA, ribosomal, 16S

KW - Salmonella infections

KW - Salmonella typhimurium

KW - sequence analysis, DNA

U2 - 10.1371/journal.pbio.0050244

DO - 10.1371/journal.pbio.0050244

M3 - Article

C2 - 17760501

VL - 5

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 10

M1 - e244

ER -