Epidemiology of the Bacteroides fragilis group in the colonic flora in 10 patients with colonic cancer

Namavar, F.; Theunissen, E. B. M.; Vught, A. M. J. J. Verweij-Van; Peerbooms, P. G. H.; Bal, Munita; Hoitsma, H. F. W.; Maclaren, D. M.

doi:10.1099/00222615-29-3-171

Cited by 54 publications

(23 citation statements)

References 12 publications

(3 reference statements)

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“…The Don system must have evolved to assist in the establishment of a specific niche in the gut or to help the organism maintain its competitive position. Several studies have indicated that B. fragilis are closely associated with the mucosa, and that they penetrate the mucus layer to bind receptors deep in the crypts (23,24). The don genes are significantly induced by a crude mixture of gastric mucin glycans and in fact, they were the most highly induced of all genes in mucin glycan medium (SI Appendix, Table S1).…”

Section: Discussionmentioning

confidence: 99%

Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections

Cao

Rocha

Smith

2014

Proc. Natl. Acad. Sci. U.S.A.

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Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. Among the Bacteroides spp. in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. This activity is mediated by an outer membrane protein complex designated as Don. Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus.

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Section: Discussionmentioning

confidence: 99%

Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections

Cao

Rocha

Smith

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Bacteroides fragilis are commensals colonizing the majority of humans and are the most frequent Bacteroides species identified at the mucosal surface of the colon where they probably contribute to intestinal homeostasis (Moore and Holdeman, 1974;Namavar et al, 1989;Hooper and Gordon, 2001;Coyne et al, 2005). Virulence of B. fragilis is ascribed, in part, to the unparalleled diversity of the polysaccharide capsule (Krinos et al, 2001) and, for ETBF strains, to the production of a zinc-dependent metalloprotease toxin termed BFT (Sears, 2001).…”

Section: Discussionmentioning

confidence: 99%

Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and γ-secretase-dependent E-cadherin cleavage

Rhee

Zhang

et al. 2007

Journal of Cell Science

210

108

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Enterotoxigenic Bacteroides fragilis – organisms that live in the colon – secrete a metalloprotease toxin, B. fragilis toxin. This toxin binds to a specific intestinal epithelial cell receptor and stimulates cell proliferation, which is dependent, in part, on E-cadherin degradation and β-catenin–T-cell-factor nuclear signaling. γ-Secretase (or presenilin-1) is an intramembrane cleaving protease and is a positive regulator of E-cadherin cleavage and a negative regulator of β-catenin signaling. Here we examine the mechanistic details of toxin-initiated E-cadherin cleavage. B. fragilis toxin stimulated shedding of cell membrane proteins, including the 80 kDa E-cadherin ectodomain. Shedding of this domain required biologically active toxin and was not mediated by MMP-7, ADAM10 or ADAM17. Inhibition of γ-secretase blocked toxin-induced proteolysis of the 33 kDa intracellular E-cadherin domain causing cell membrane retention of a distinct β-catenin pool without diminishing toxin-induced cell proliferation. Unexpectedly, γ-secretase positively regulated basal cell proliferation dependent on the β-catenin–T-cell-factor complex. We conclude that toxin induces step-wise cleavage of E-cadherin, which is dependent on toxin metalloprotease and γ-secretase. Our results suggest that differentially regulated β-catenin pools associate with the E-cadherin–γ-secretase adherens junction complex; one pool regulated by γ-secretase is important to intestinal epithelial cell homeostasis.

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“…Inflammation of the intestinal tract caused by Campylobacter jejuni, Helicobacter pylori, and many other pathogens results in increased levels of oxidative stress within the epithelial layer and the intestinal tract (46)(47)(48)(49). B. fragilis is closely associated with the intestinal epithelium, which has been shown to incur significant DNA damage from reactive oxygen species from the host immune response (47,50,51). Additionally, it has been shown that an oxygen concentration gradient exists extending out from the epithelial surface, so that B. fragilis may be exposed to an environment with as much as 8% oxygen, depending on the precise site of colonization (51,52).…”

Section: Discussionmentioning

confidence: 99%

Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

2015

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Bacteroides fragilis is a Gram-negative anaerobe and member of the human intestinal tract microbiome, where it plays many beneficial roles. However, translocation of the organism to the peritoneal cavity can lead to peritonitis, intra-abdominal abscess formation, bacteremia, and sepsis. During translocation, B. fragilis is exposed to increased oxidative stress from the oxygenated tissues of the peritoneal cavity and the immune response. In order to survive, B. fragilis mounts a robust oxidative stress response consisting of an acute and a prolonged oxidative stress (POST) response. This report demonstrates that the ability to induce high levels of resistance to tert-butyl hydroperoxide (tBOOH) after extended exposure to air can be linked to the POST response. Disk diffusion assays comparing the wild type to a ⌬dps mutant and a ⌬dps ⌬bfr mutant showed greater sensitivity of the mutants to tBOOH after exposure to air, suggesting that Dps and DpsL play a role in the resistance phenotype. Complementation studies with dps or bfr (encoding DpsL) restored tBOOH resistance, suggesting a role for both of these ferritin-family proteins in the response. Additionally, cultures treated with the iron chelator dipyridyl were not killed by tBOOH, indicating Dps and DpsL function by sequestering iron to prevent cellular damage. An in vivo animal model showed that the ⌬dps ⌬bfr mutant was attenuated, indicating that management of iron is important for survival within the abscess. Together, these data demonstrate a role for Dps and DpsL in the POST response which mediates survival in vitro and in vivo. IMPORTANCEB. fragilis is the anaerobe most frequently isolated from extraintestinal opportunistic infections, but there is a paucity of information about the factors that allow this organism to survive outside its normal intestinal environment. This report demonstrates that the iron storage proteins Dps and DpsL protect against oxidative stress and that they contribute to survival both in vitro and in vivo. Additionally, this work demonstrates an important role for the POST response in B. fragilis survival and provides insight into the complex regulation of this response. Bacteroides spp. are members of the normal intestinal microbiome of humans. The intestine is a consistent and favorable environment that provides continuous access to nutrient sources for these strictly anaerobic organisms. Bacteroides spp. play many important roles in maintaining a healthy intestinal tract, such as polysaccharide degradation, protection of the gut epithelia from colonization by pathogenic bacteria, development of the intestinal tract, maturation of the mucosal and systemic immune systems, and transformation of toxic and mutagenic compounds (1-4). However, when the integrity of the intestinal wall is breached due to trauma, abdominal surgery, or diseases such as appendicitis, perforated ulcer, diverticulitis, and colon cancer, translocation of the normal flora into the peritoneal cavity can result in peritonitis and establishment of an intr...

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Epidemiology of the Bacteroides fragilis group in the colonic flora in 10 patients with colonic cancer

Cited by 54 publications

References 12 publications

Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections

Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections

Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and γ-secretase-dependent E-cadherin cleavage

Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

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