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 - 2007/10/1
Y1 - 2007/10/1
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-HACL4-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-HACL4-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.
UR - http://www.scopus.com/inward/record.url?scp=35649026345&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.0050244
DO - 10.1371/journal.pbio.0050244
M3 - Article
C2 - 17760501
AN - SCOPUS:35649026345
SN - 1544-9173
VL - 5
SP - 2177
EP - 2189
JO - PLoS Biology
JF - PLoS Biology
IS - 10
ER -