Salmonella Enterica Serovar Typhimurium Exploits Inflammation to Compete with the Intestinal Microbiota

Overview

Journal PLoS Biol

Specialty Biology

Date 2007 Sep 1

PMID 17760501

Citations 565

Authors

Barbel 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

Affiliations

Soon will be listed here.

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.

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References

Rabbani G, Albert M, Rahman H, Islam M, Mahalanabis D, Kabir I . Development of an improved animal model of shigellosis in the adult rabbit by colonic infection with Shigella flexneri 2a. Infect Immun. 1995; 63(11):4350-7. PMC: 173619. DOI: 10.1128/iai.63.11.4350-4357.1995. View

Samuel B, Gordon J . A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism. Proc Natl Acad Sci U S A. 2006; 103(26):10011-6. PMC: 1479766. DOI: 10.1073/pnas.0602187103. View

Bader M, Sanowar S, Daley M, Schneider A, Cho U, Xu W . Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell. 2005; 122(3):461-72. DOI: 10.1016/j.cell.2005.05.030. View

Sonnenburg J, Xu J, Leip D, Chen C, Westover B, Weatherford J . Glycan foraging in vivo by an intestine-adapted bacterial symbiont. Science. 2005; 307(5717):1955-9. DOI: 10.1126/science.1109051. View

Gophna U, Sommerfeld K, Gophna S, Doolittle W, Veldhuyzen van Zanten S . Differences between tissue-associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis. J Clin Microbiol. 2006; 44(11):4136-41. PMC: 1698347. DOI: 10.1128/JCM.01004-06. View

Dann S, Eckmann L . Innate immune defenses in the intestinal tract. Curr Opin Gastroenterol. 2007; 23(2):115-20. DOI: 10.1097/MOG.0b013e32803cadf4. View

Ashelford K, Chuzhanova N, Fry J, Jones A, Weightman A . New screening software shows that most recent large 16S rRNA gene clone libraries contain chimeras. Appl Environ Microbiol. 2006; 72(9):5734-41. PMC: 1563593. DOI: 10.1128/AEM.00556-06. View

Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W . Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993; 75(2):263-74. DOI: 10.1016/0092-8674(93)80068-p. View

Barthel M, Hapfelmeier S, Quintanilla-Martinez L, Kremer M, Rohde M, Hogardt M . Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun. 2003; 71(5):2839-58. PMC: 153285. DOI: 10.1128/IAI.71.5.2839-2858.2003. View

10.

Ashelford K, Chuzhanova N, Fry J, Jones A, Weightman A . At least 1 in 20 16S rRNA sequence records currently held in public repositories is estimated to contain substantial anomalies. Appl Environ Microbiol. 2005; 71(12):7724-36. PMC: 1317345. DOI: 10.1128/AEM.71.12.7724-7736.2005. View

11.

Uzzau S, Bossi L, Figueroa-Bossi N . Differential accumulation of Salmonella[Cu, Zn] superoxide dismutases SodCI and SodCII in intracellular bacteria: correlation with their relative contribution to pathogenicity. Mol Microbiol. 2002; 46(1):147-56. DOI: 10.1046/j.1365-2958.2002.03145.x. View

12.

Coburn B, Li Y, Owen D, Vallance B, Finlay B . Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis. Infect Immun. 2005; 73(6):3219-27. PMC: 1111876. DOI: 10.1128/IAI.73.6.3219-3227.2005. View

13.

Stecher B, Paesold G, Barthel M, Kremer M, Jantsch J, Stallmach T . Chronic Salmonella enterica serovar Typhimurium-induced colitis and cholangitis in streptomycin-pretreated Nramp1+/+ mice. Infect Immun. 2006; 74(9):5047-57. PMC: 1594839. DOI: 10.1128/IAI.00072-06. View

14.

Szilagyi A, Gerson M, Mendelson J, Yusuf N . Salmonella infections complicating inflammatory bowel disease. J Clin Gastroenterol. 1985; 7(3):251-5. DOI: 10.1097/00004836-198506000-00013. View

15.

Hapfelmeier S, Stecher B, Barthel M, Kremer M, Muller A, Heikenwalder M . The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and MyD88-independent mechanisms. J Immunol. 2005; 174(3):1675-85. DOI: 10.4049/jimmunol.174.3.1675. View

16.

Edgar R . MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics. 2004; 5:113. PMC: 517706. DOI: 10.1186/1471-2105-5-113. View

17.

Ley R, Backhed F, Turnbaugh P, Lozupone C, Knight R, Gordon J . Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005; 102(31):11070-5. PMC: 1176910. DOI: 10.1073/pnas.0504978102. View

18.

Turnbaugh P, Ley R, Mahowald M, Magrini V, Mardis E, Gordon J . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006; 444(7122):1027-31. DOI: 10.1038/nature05414. View

19.

Khan M, Ma C, Knodler L, Valdez Y, Rosenberger C, Deng W . Toll-like receptor 4 contributes to colitis development but not to host defense during Citrobacter rodentium infection in mice. Infect Immun. 2006; 74(5):2522-36. PMC: 1459750. DOI: 10.1128/IAI.74.5.2522-2536.2006. View

20.

Cole J, Chai B, Farris R, Wang Q, Kulam S, McGarrell D . The Ribosomal Database Project (RDP-II): sequences and tools for high-throughput rRNA analysis. Nucleic Acids Res. 2004; 33(Database issue):D294-6. PMC: 539992. DOI: 10.1093/nar/gki038. View