Regulated Virulence Controls the Ability of a Pathogen to Compete with the Gut Microbiota

By N. Kamada, Yun-Gi Kim, H. P. Sham, B. Vallance, J. Puente, E. Martens, G. Núñez. Science, 2012

631 citations recorded by the source corpus.

Establishing an Enteric Infection Complex and highly regulated interactions are required to keep the peace between the bacteria that reside in our gut and the immune system. How do pathogenic bacteria, such as the strains of Escherichia coli that cause gastroenteritis, get a foothold to establish an infection, and what is the role of resident bacteria in this process? Kamada et al. (p. 1325, published online 10 May; see the Perspective by Sperandio) infected mice orally with Citrobacter rodentium and found that mice with normal commensal microflora, which were better able to contain the infection than mice that lacked the commensals, which were not able to clear the infection. Virulence genes and nutritional requirements determine the course of a gastroenteric bacterial infection in mice. The virulence mechanisms that allow pathogens to colonize the intestine remain unclear. Here, we show that germ-free animals are unable to eradicate Citrobacter rodentium, a model for human infections with attaching and effacing bacteria. Early in infection, virulence genes were expressed and required for pathogen growth in conventionally raised mice but not germ-free mice. Virulence gene expression was down-regulated during the late phase of infection, which led to relocation of the pathogen to the intestinal lumen where it was outcompeted by commensals. The ability of commensals to outcompete C. rodentium was determined, at least in part, by the capacity of the pathogen and commensals to grow on structurally similar carbohydrates. Thus, pathogen colonization is controlled by bacterial virulence and through competition with metabolically related commensals.

Subfields: Endocrinology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d7b9d7fbcc268bd6c48d6cf3733217fb228fd900

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Citations in the corpus

The human microbiome (2017, neutral): “Еще одной важной ролью микробиоты кишечника является формирование колонизационной резистентности, предотвращающей заселение кишечника патогенными микроорганизмами, например, за счет конкуренции за питательные вещества [14].”
A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility (2016, positive): “The FF diet was manufactured by Teklad/Envigo (WI, USA) and, as previously e5 Cell 167, 1339–1353.e1–e12, November 17, 2016 described (TD.140343) (Kamada et al., 2012), consisted of a modified version of Harlan TD.08810 in which starch and maldodextrin were replaced with glucose.”
Computational meta'omics for microbial community studies (2013, background): “Examples include the ability of the commensal microbiome to eradicate Citrobacter rodentium infections (to which germ-free mice are susceptible (Kamada et al , 2012)) and the development of inﬂammatory colitis and colorectal cancer (Garrett et al , 2010).”
NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. (2014, neutral): “Notably, other NLRP6 regulatory effects may contribute to containment of intestinal infection, such as thosemediated by regulation of microbiota composition, recently highlighted to be central in regulation of C. rodentium clearance (Kamada et al., 2012).”
Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells (2015, neutral): “The C. rodentium Deae and E. coli O157:H7 Dstx1Dstx2 mutant strains have been described previously (Kamada et al., 2012; Nagano et al., 2003).”
Colonocyte metabolism shapes the gut microbiota (2018, background): “rodentium uses its virulence factors to intimately attach to the colonic surface, which enables the pathogen to compete with the gut microbiota (81, 82).”
Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease (2017, background): “rodentium) from the mouse gut, the microbiota act in concert with the host immune system (47, 48), and competition”
Mechanisms of inflammation-driven bacterial dysbiosis in the gut (2016, neutral): “Of note, some pathogens within the family Enterobacteriaceae, namely Citrobacter rodentium and Salmonella, initially utilize virulence factors to induce intestinal inflammation, which subsequently confers a growth advantage for these pathogens in the intestinal lumen.(32,34,52) In addition, oral inf”