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-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.

Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

“…Twelve-week-old FVB/N CEABAC10 transgenic male mice (body weight, 26 to 28 g) that expressed human CEACAM6 were first pretreated orally with the broad-spectrum antibiotic streptomycin (5 mg per mouse administered intragastrically) to disrupt the normal resident bacterial flora in the intestinal tract (34) and then orally challenged with 10 9 bacteria 24 h later. The animals received an extremely low dose of 0.25% (wt/vol) dextran sulfate sodium (DSS; molecular mass, 36,000 to 50,000 Da; MP Biomedicals) in their drinking water starting 3 days before infection to increase the bacteria's accessibility to the surface of the epithelial layer.…”

Impact of Usp18 and IFN signaling in Salmonella-induced typhlitis

“…These data are in agreement with previous work showing signs of recovery (reappearance of the intestinal epithelium and goblet cells) at day 20 post infection in 129Sv/Ev mice infected with Salmonella Typhimurium. 18 Overall, the pathologic scores observed on the mixed background of ITY9 mice were higher than those observed in pure 129S6 or C57BL/6J background demonstrating the impact of the background on the expression of the phenotype.…”

“…8 Other groups have compared the impact of the genetic background on disease manifestation and found no difference between the C57BL/6J and 129Sv/Ev background early after infection. 18 These discrepancies could be explained by the fact that the different studies used different 129 substrains; although closely related, different 129 substrains still present an important genetic diversity. As an example, we have identified 19 545 single-nucleotide polymorphisms between 129S1 and 129X1 using the Diversity Mouse Genotyping Array (unpublished data).…”

“…We also demonstrate that there is a threshold of type I IFN activation that is favorable for bacterial clearance beyond which the stimulatory effect is detrimental to the host. 16 As the Usp18 ity9/ity9 mutant showed increased inflammation because of the increased type I IFN signaling and that inflammation was shown to be either protective 8 or detrimental 18 in Salmonella-induced colitis in mice pretreated with streptomycin, we sought to determine the impact of the Usp18 mutation on Salmonella susceptibility and the intestinal inflammation using the natural route of infection. In the current paper, we report that mutation within USP18 affects the outcome of Salmonellainduced typhlitis.…”

Reciprocity in Microbiome and Immune System Interactions and its Implications in Disease and Health

“…Elimination of gut normal microflora with antibiotics contributes to high susceptibility of mice to experimental colitis induction with dextran sodium sulfate (DSS) [43]. An entropathogenic bacterium Salmonella enterica inhibits the growth of microbiota in the gut and subsequently predisposes mice to colitis development [44]. Alteration of the gut microbiome by antibiotics in humnas can lead to the development of pathogenic Clostridium difficile infection [45].…”