scholarly journals Host Susceptibility to the Attaching and Effacing Bacterial Pathogen Citrobacter rodentium

2003 ◽  
Vol 71 (6) ◽  
pp. 3443-3453 ◽  
Author(s):  
Bruce A. Vallance ◽  
Wanyin Deng ◽  
Kevan Jacobson ◽  
B. Brett Finlay
Keyword(s):  
Bacterial Translocation ◽  
Cell Apoptosis ◽  
Bacterial Colonization ◽  
Bacterial Load ◽  
Crypt Cell ◽  
Host Susceptibility ◽  
Mouse Strains ◽  
Citrobacter Rodentium ◽  
Mesenteric Lymph Nodes ◽  
Susceptible Mouse

ABSTRACT Many studies have shown that genetic susceptibility plays a key role in determining whether bacterial pathogens successfully infect and cause disease in potential hosts. Surprisingly, whether host genetics influence the pathogenesis of attaching and effacing (A/E) bacteria such as enteropathogenic and enterohemorrhagic Escherichia coli has not been examined. To address this issue, we infected various mouse strains with Citrobacter rodentium, a member of the A/E pathogen family. Of the strains tested, the lipopolysaccharide (LPS) nonresponder C3H/HeJ mouse strain experienced more rapid and extensive bacterial colonization than did other strains. Moreover, the high bacterial load in these mice was associated with accelerated crypt hyperplasia, mucosal ulceration, and bleeding, together with very high mortality rates. Interestingly, the basis for the increased susceptibility was not due to LPS hyporesponsiveness, as the genetically related but LPS-responsive C3H/HeOuJ and C3H/HeN mouse strains were also susceptible to infection. Analysis of the intestinal pathology in these susceptible strains revealed significant crypt epithelial cell apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end label staining) as well as bacterial translocation to the mesenteric lymph nodes. Further studies with infection of SCID (T- and B-lymphocyte-deficient) C3H/HeJ mice demonstrated that loss of lymphocytes had no effect on bacterial numbers but did reduce crypt cell apoptosis and delayed mortality. These studies thus identify the adaptive immune system, crypt cell apoptosis, and bacterial translocation but not LPS responsiveness as contributing to the tissue pathology and mortality seen during C. rodentium infection of highly susceptible mouse strains. Determining the basis for these strains' susceptibility to intestinal colonization by an A/E pathogen will be the focus of future studies.

scholarly journals A52 BUTYRATE SUPPLEMENTATION AMELIORATES DAMAGE CAUSED BY ENTERIC CITROBACTER RODENTIUM INFECTION

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 61-62
Author(s):  
L S Celiberto ◽  
G Healey ◽  
J Xu ◽  
L Xia ◽  
B Vallance
Keyword(s):  
Butyric Acid ◽  
Tissue Damage ◽  
Intestinal Inflammation ◽  
Bacterial Colonization ◽  
Clinical Signs ◽  
Host Susceptibility ◽  
Mucus Layer ◽  
Citrobacter Rodentium ◽  
Oral Gavage ◽  
Intestinal Mucus

Abstract Background Patients with inflammatory bowel disease (IBD) often display a dysbiotic microbiome as well as a defective intestinal mucus layer, which appears thinner and more penetrable than the mucus layer of healthy subjects. Tributyrin (TB), a prodrug of butyric acid, has shown beneficial effects in models of IBD due to its anti-inflammatory effects. We previously showed that mice lacking the major intestinal mucin Muc2 (Muc2-/-) or lacking the “Core1” enzyme responsible for glycosylating Muc2 (C1galt1-/-) were highly susceptible to infection by Citrobacter rodentium, a murine model of intestinal inflammation. Aims The study explored the role of gut mucus in providing host defense against C. rodentium, as well as the effects of TB supplementation in the prevention of mucosal damage in this model. Methods Six to ten week old wildtype (WT), Muc2-/-, flox control (C1galt1f/f) and C1galt1-/- mice were infected with C. rodentium (∼2.5 × 108 CFU) by oral gavage. For TB supplementation experiments, mice received 100µL of TB or glycerol as a control by oral gavage every other day starting on day 1 post infection. Mice were monitored daily throughout the experiment and were euthanized at day 6 of infection. Several tissues of interest were collected to verify bacterial colonization in the gut and at systemic sites as well as histological tissue damage. Cecal contents were collected for the analysis of short chain fatty acids, while blood was collected by cardiac puncture after oral gavage with FITC-dextran to measure intestinal permeability. Results While WT and C1galt1f/f mice were only modestly susceptible to C. rodentium infection, Muc2-/- and C1galt1-/- mice displayed dramatically (100 fold) increased pathogen burdens, significantly greater intestinal macroscopic and histopathology scores, and heightened barrier disruption as compared to controls. Moreover, Muc2-/- and C1galt1-/- mice showed significantly lower levels of butyric acid as compared to control mice under baseline conditions. Interestingly, when supplemented with TB, Muc2-/- and C1galt1-/- proved less susceptible to C. rodentium infection, as indicated by reduced weight loss and clinical signs of colitis, while pathogen burdens were greatly reduced as was histological tissue damage, and epithelial barrier dysfunction. The same protection was conferred when TB was administered as a dietary supplementation, thus confirming its beneficial effect in protecting mice against C. rodentium infection. Conclusions These findings demonstrate that intestinal mucus controls host susceptibility to C. rodentium infection via control over butyrate levels, and highlight the need to explore the mechanisms by which gut mucus modulates the resident microbiota and its metabolites. Funding Agencies CCC, CIHR

scholarly journals Time Course and Host Responses to Escherichia coli Urinary Tract Infection in Genetically Distinct Mouse Strains

1998 ◽  
Vol 66 (6) ◽  
pp. 2798-2802 ◽  
Author(s):  
Walter J. Hopkins ◽  
Annette Gendron-Fitzpatrick ◽  
Edward Balish ◽  
David T. Uehling
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Host Defense ◽  
Time Course ◽  
Bacterial Colonization ◽  
Infection Intensity ◽  
Host Susceptibility ◽  
Mouse Strains ◽  
Specific Host ◽  
Tract Infections

ABSTRACT Recurrent urinary tract infections (UTIs) are a significant clinical problem for many women; however, host susceptibility factors have not been completely defined. The mouse model of induced UTI provides an experimental environment in which to identify specific host characteristics that are important in initial bacterial colonization of the urinary tract and in resolution of an infection. This study examined initial susceptibility, bacterial clearance, and host defense mechanisms during induction and resolution of Escherichia coli UTIs in genetically distinct strains of mice. Of the ten inbred strains tested, six (BALB/c, C3H/HeN, C57BL/6, DBA.1, DBA.2, and AKR) showed progressive resolution of bladder infections over a 14-day period. A constant, low-level bladder infection was observed in SWR and SJL mice. High bladder infection levels persisted over the 14-day study period in C3H/HeJ and C3H/OuJ mice. Kidney infection levels generally correlated with bladder infection levels, especially in C3H/HeJ and C3H/OuJ mice, the two most susceptible strains, in which infections became more severe with time after challenge. The degree of inflammation in bladder and kidneys, as well as antibody-forming cell responses, positively correlated with infection intensity in all strains except C3H/HeJ, which had minimal inflammation despite high infection levels. These results demonstrate two important aspects of host defense against UTI. First, the innate immune response to an infection in the bladder or kidneys consists primarily of local inflammation, which is followed by an adaptive response characterized in part by an antibody response to the infecting bacteria. Second, a UTI will be spontaneously resolved in most cases; however, in mice with specific genetic backgrounds, a UTI can persist for an extended length of time. The latter result strongly suggests that the presence or absence of specific host genes will determine how effectively an E. coli UTI will be resolved.

Persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation

2001 ◽  
Vol 281 (3) ◽  
pp. G635-G644 ◽  
Author(s):  
Samuel Asfaha ◽  
Wallace K. MacNaughton ◽  
Caroline B. Appleyard ◽  
Kris Chadee ◽  
John L. Wallace
Keyword(s):  
Bacterial Translocation ◽  
Intestinal Inflammation ◽  
Bacterial Colonization ◽  
Bacterial Load ◽  
Phosphodiesterase Inhibitor ◽  
Trinitrobenzene Sulfonic Acid ◽  
Susceptibility To Infection ◽  
Epithelial Secretion ◽  
Epithelial Dysfunction

Epithelial secretion may play an important role in reducing bacterial colonization and translocation in intestine. If so, secretory dysfunction could result in increased susceptibility to infection and inflammation. We investigated whether long-term colonic secretory dysfunction occurs after a bout of colitis and if this is accompanied by an increase in bacterial colonization and translocation. Rats were studied 6 wk after induction of colitis with trinitrobenzene sulfonic acid when inflammation had completely resolved, and epithelial permeability was normal. Intestinal loops were stimulated with either Clostridium difficile toxin A or a phosphodiesterase inhibitor. In vitro, colonic tissue from previously sensitized rats was exposed to antigen (ovalbumin). Secretory responses to all three stimuli were suppressed in rats that had previously had colitis. These rats exhibited increased (16-fold) numbers of colonic aerobic bacteria and increased (>3-fold) bacterial translocation, similar to results in rats studied after resolution of enteritis. Postcolitis bacterial translocation was prevented by daily treatment with an inhibitor of inducible nitric oxide synthase. This study demonstrates that intestinal inflammation results in prolonged impairment of colonic epithelial secretion, which may contribute to increases in bacterial load and bacterial translocation. Epithelial dysfunction of this type could underlie an increased propensity for further bouts of inflammation, a hallmark of diseases such as inflammatory bowel disease.

scholarly journals Citrobacter rodentium lifA/efa1 Is Essential for Colonic Colonization and Crypt Cell Hyperplasia In Vivo

2005 ◽  
Vol 73 (3) ◽  
pp. 1441-1451 ◽  
Author(s):  
Jan-Michael A. Klapproth ◽  
Maiko Sasaki ◽  
Melanie Sherman ◽  
Brian Babbin ◽  
Michael S. Donnenberg ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bacterial Colonization ◽  
Crypt Cell ◽  
Enteric Infection ◽  
Citrobacter Rodentium ◽  
Wild Type ◽  
E Coli ◽  
Epithelial Regeneration ◽  
Crypt Cell Proliferation

ABSTRACT Previously, we have identified a large gene (lifA, for lymphocyte inhibitory factor A) in enteropathogenic Escherichia coli (EPEC) encoding a protein termed lymphostatin that suppresses cytokine expression in vitro. This protein also functions as an adhesion factor for enterohemorrhagic E. coli (EHEC) and Shiga toxin-producing E. coli and is alternatively known as efa1 (EHEC factor for adherence 1). The lifA/efa1 gene is also present in Citrobacter rodentium, an enteric pathogen that causes a disease termed transmissible murine colonic hyperplasia (TMCH), which induces colitis and massive crypt cell proliferation, in mice. To determine if lifA/efa1 is required for C. rodentium-induced colonic pathology in vivo, three in-frame mutations were generated, disrupting the glycosyltransferase (GlM12) and protease (PrMC31) motifs and a domain in between that does not encode any known activity (EID3). In contrast to infection with wild-type C. rodentium, that with any of the lifA/efa1 mutant strains did not induce weight loss or TMCH. Enteric infection with motif mutants GlM12 and PrM31 resulted in significantly reduced colonization counts during the entire 20-day course of infection. In contrast, EID3 was indistinguishable from the wild type during the initial colonic colonization, but cleared rapidly after day 8 of the infection. The colonic epithelium of all infected mice displayed increased epithelial regeneration. However, significantly increased regeneration was observed by day 20 only in mice infected with the wild-type in comparison to those infected with lifA/efa1 mutant EID3. In summary, lifA/efa1 is a critical gene outside the locus for enterocyte effacement that regulates bacterial colonization, crypt cell proliferation, and epithelial cell regeneration.

scholarly journals Bifidobacteria may be beneficial to intestinal microbiota and reduction of bacterial translocation in mice following ischaemia and reperfusion injury

2012 ◽  
Vol 109 (11) ◽  
pp. 1990-1998 ◽  
Author(s):  
Honggang Wang ◽  
Wei Zhang ◽  
Lugen Zuo ◽  
Weiming Zhu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Intestinal Microbiota ◽  
Bacterial Translocation ◽  
Cell Apoptosis ◽  
Intestinal Barrier ◽  
Peroral Administration ◽  
Barrier Dysfunction ◽  
Mesenteric Lymph Nodes ◽  
Ischaemia And Reperfusion ◽  
Epithelial Cell Apoptosis

The aim of the present study was to determine the effect of peroral bifidobacteria on the intestinal microbiota, barrier function and bacterial translocation (BT) in a mouse model of ischaemia and reperfusion (I/R) injury. A total of twenty-four male BALB/c mice were randomly allocated into three groups: (1) sham-operated, (2) I/R and (3) I/R injury and bifidobacteria pretreatment (109colony-forming units/d). Bifidobacteria were administered daily intragastrically for 2 weeks before induction of I/R. Subsequently, samples of caecal content, intestinal mucosa, ileal segments, blood, mesenteric lymph nodes (MLN) and distant organs (liver, spleen and kidney) were prepared for examination. In the I/R model, barrier dysfunction (caecal microbiota dysbiosis, disruption of tight junction (TJ), increased epithelial cell apoptosis, disruption of mucosa and multiple erosions) in the intestine was observed, associated with increased BT to extraintestinal sites. The ratio of BT to MLN and distant organs in mice exposed to I/R injury was 62·5 %, which was significantly higher than the sham-operated group. However, pretreatment of animals with bifidobacteria prevented I/R-induced BT, reduced pro-inflammatory cytokine release, the levels of endotoxin, intestinal epithelial cell apoptosis, disruption of TJ and increased the concentration of SCFA, resulting in recovered microbiota and mucosal integrity. Bifidobacteria may be beneficial in reducing BT in I/R injury of mice. Therefore, peroral administration of bifidobacteria is a potential strategy to prevent I/R-induced BT and intestinal barrier dysfunction.

scholarly journals Monoassociation of Preterm Germ-Free Piglets with Bifidobacterium animalis Subsp. lactis BB-12 and Its Impact on Infection with Salmonella Typhimurium

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 183
Author(s):  
Alla Splichalova ◽  
Sharon M. Donovan ◽  
Helena Tlaskalova-Hogenova ◽  
Zbynek Stranak ◽  
Zdislava Splichalova ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Bacterial Translocation ◽  
Bacterial Colonization ◽  
Plasma Concentrations ◽  
Clinical Signs ◽  
Mesenteric Lymph Nodes ◽  
Germ Free ◽  
Bifidobacterium Animalis ◽  
Tnf Α ◽  
Gnotobiotic Piglets

Preterm germ-free piglets were monoassociated with probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB12) to verify its safety and to investigate possible protection against subsequent infection with Salmonella Typhimurium strain LT2 (LT2). Clinical signs of salmonellosis, bacterial colonization in the intestine, bacterial translocation to mesenteric lymph nodes (MLN), blood, liver, spleen, and lungs, histopathological changes in the ileum, claudin-1 and occludin mRNA expression in the ileum and colon, intestinal and plasma concentrations of IL-8, TNF-α, and IL-10 were evaluated. Both BB12 and LT2 colonized the intestine of the monoassociated piglets. BB12 did not translocate in the BB12-monoassociated piglets. BB12 was detected in some cases in the MLN of piglets, consequently infected with LT2, but reduced LT2 counts in the ileum and liver of these piglets. LT2 damaged the luminal structure of the ileum, but a previous association with BB12 mildly alleviated these changes. LT2 infection upregulated claudin-1 mRNA in the ileum and colon and downregulated occludin mRNA in the colon. Infection with LT2 increased levels of IL-8, TNF-α, and IL-10 in the intestine and plasma, and BB12 mildly downregulated them compared to LT2 alone. Despite reductions in bacterial translocation and inflammatory cytokines, clinical signs of LT2 infection were not significantly affected by the probiotic BB12. Thus, we hypothesize that multistrain bacterial colonization of preterm gnotobiotic piglets may be needed to enhance the protective effect against the infection with S. Typhimurium LT2.

Bacterial translocation can increase plasma corticosterone and brain catecholamine and indoleamine metabolism

2000 ◽  
Vol 279 (6) ◽  
pp. R2164-R2172 ◽  
Author(s):  
Tetsuya Ando ◽  
Rhonda F. Brown ◽  
Rodney D. Berg ◽  
Adrian J. Dunn
Keyword(s):  
Hpa Axis ◽  
Bacterial Translocation ◽  
Plasma Corticosterone ◽  
Potential Contribution ◽  
Mesenteric Lymph Nodes ◽  
Gram Positive Bacteria ◽  
Amine Metabolism ◽  
Viable Bacteria ◽  
Neurochemical Changes ◽  
Indoleamine Metabolism

The potential contribution of stress-induced bacterial translocation to the activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and brain biogenic amines was assessed. Mice were restrained for various periods, and brain concentrations of tryptophan, catecholamines, serotonin, and their metabolites, plasma corticosterone, and the translocation of viable bacteria from the gastrointestinal tract to the mesenteric lymph nodes, spleen, and liver were measured. Restraint induced the translocation of indigenous gram-positive bacteria in only a small proportion of animals, but translocation of gram-negative bacteria did not occur. Restraint induced short-lived increases in plasma corticosterone and brain amine metabolism, whereas bacterial translocation was slower and persisted long after the HPA axis and neurochemical responses had dissipated. When mice were infected with Salmonella typhimurium, spontaneous translocation occurred and plasma corticosterone, interleukin-6 concentrations, and brain catecholamine and indoleamine metabolism were elevated. These findings indicate that the translocation of indigenous gastrointestinal bacteria did not contribute to the HPA axis and neurochemical changes induced by restraint. However, translocation of nonindigenous S. typhimurium with or without restraint did induce HPA and neurochemical responses.

scholarly journals Citrobacter rodentium lifA/efa1 Is Essential for Colonic Colonization and Crypt Cell Hyperplasia In Vivo

2005 ◽  
Vol 73 (5) ◽  
pp. 3196-3196 ◽  
Author(s):  
Jan-Michael A. Klapproth ◽  
Maiko Sasaki ◽  
Melanie Sherman ◽  
Brian Babbin ◽  
Michael S. Donnenberg ◽  
...  
Keyword(s):  
Crypt Cell ◽  
Citrobacter Rodentium ◽  
Cell Hyperplasia

scholarly journals Influence of the Bcg Locus on Natural Resistance to Primary Infection with the Facultative Intracellular Bacterium Francisella tularensis in Mice

2000 ◽  
Vol 68 (3) ◽  
pp. 1480-1484 ◽  
Author(s):  
Hana Kovářová ◽  
Lenka Hernychová ◽  
Marián Hajdúch ◽  
M. Šírová ◽  
Aleš Macela
Keyword(s):  
Francisella Tularensis ◽  
Bacterial Colonization ◽  
Phenotypic Expression ◽  
Interleukin 10 ◽  
Natural Resistance ◽  
Mouse Strains ◽  
Oxygen Intermediates ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Resistance To Infection

ABSTRACT The implication of the Bcg locus in the control of natural resistance to infection with a live vaccine strain (LVS) of the intracellular pathogen Francisella tularensis was studied. Analysis of phenotypic expression of natural resistance and susceptibility was performed using mouse strains congenic at theBcg locus. Comparison of the kinetics of bacterial colonization of spleen showed that B10.A.Bcg(r) mice were extremely susceptible during early phases of primary sublethal infection, while their congenic C57BL/10N [Bcg(s)] counterparts could be classified as resistant to F. tularensis LVS infection according to the 2-log-lower bacterial CFU within the tissue as long as 5 days after infection. Different phenotypes of Bcg congenic mice were associated with differential expression of the cytokines tumor necrosis factor alpha, interleukin-10, and gamma interferon and production of reactive oxygen intermediates. These results strongly suggest that the Bcglocus, which is close or identical to the Nramp1 gene, controls natural resistance to infection by F. tularensisand that its effect is the opposite of that observed for otherBcg-controlled pathogens.

Sign in / Sign up

Export Citation Format

Share Document