Incidence of enteric bacterial infections complicating Clostridium difficile infection (CDI)

The purpose of this study was to assess whether C. difficile infection (CDI) increases the risk of bacteremia or E. coli infection. The first specific aim of this study was to study the incidence of post C. difficile bacteremia in CDI patients stratified by disease severity vs. controls. The second specific aim was to study the incidence of post C. difficile E. coli infection from normally sterile sites stratified by disease severity vs. controls. This was a retrospective case case control study. The cases came from an ongoing prospective cohort study of CDI. Case group 1 were patients with mild to moderate CDI. Case group 2 were patients who had severe CDI. Controls were hospitalized patients given broad spectrum antibiotics that did not develop CDI. Controls were matched by age (±10 years) and duration of hospital visit (±1 week). 191 cases were selected from the cohort study and 191 controls were matched to the cases. Patients were followed up to 60 days after the initial diagnosis of CDI and assessed for bacteremia and E. coli infections. The Zar score was used to determine the severity of the CDI. Stata 11 was used to run all analyses. ^ The risk of non staphylococcal bacteremia after diagnosis of CDI was higher compared to controls (14% and 7% respectively, OR: 2.27; 95% CI:1.07-5.01, p=0.028). The risk of getting an E.coli infection was higher in cases than in controls (13% and 9% respectively although the results were not statistically significant (OR:1.4; 95% CI:0.38-5.59;p=0.32). Rates of non-staphylococcal bacteremia and E. coli infection did not differ cased on CDI severity. ^ This study showed that the risk of developing non-staphylococcus bacteremia was higher in patients with CDI compared to matched controls. The findings supported the hypothesis that CDI increases the risk of bacterial translocation specifically leading to the development of bacteremia.^

Regulation of hepatic cytochrome P450 expression in mice with intestinal or systemic infections of citrobacter rodentium.

We reported previously that infection of C3H/HeOuJ (HeOu) mice with the murine intestinal pathogen Citrobacter rodentium caused a selective modulation of hepatic cytochrome P450 (P450) gene expression in the liver that was independent of the Toll-like receptor 4. However, HeOu mice are much more sensitive to the pathogenic effects of C. rodentium infection, and the P450 down-regulation was associated with significant morbidity in the animals. Here, we report that oral infection of C57BL/6 mice with C. rodentium, which produced only mild clinical signs and symptoms, produced very similar effects on hepatic P450 expression in this strain. As in HeOu mice, CYP4A mRNAs and proteins were among the most sensitive to down-regulation, whereas CYP4F18 was induced. CYP2D9 mRNA was also induced 8- to 9-fold in the C57BL/6 mice. The time course of P450 regulation followed that of colonic inflammation and bacterial colonization, peaking at 7 to 10 days after infection and returning to normal at 15 to 24 days as the infection resolved. These changes also correlated with the time course of significant elevations in the serum of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha, as well as of interferon-gamma and IL-2, with serum levels of IL-6 being markedly higher than those of the other cytokines. Intraperitoneal administration of C. rodentium produced a rapid down-regulation of P450 enzymes that was quantitatively and qualitatively different from that of oral infection, although CYP2D9 was induced in both models, suggesting that the effects of oral infection on the liver are not due to bacterial translocation.

Syntaxin 6- and microtubule- mediated intracellular trafficking contributes to Golgi and nuclear translocation of EGFR

Receptor-mediated endocytosis is well known for its degradation and recycling trafficking. Recent evidence shows that these cell surface receptors translocate from cell surface to different cellular compartments, including the Golgi, mitochondria, endoplasmic reticulum (ER), and the nucleus to regulate physiological and pathological functions. Although some trafficking mechanisms have been resolved, the mechanism of intracellular trafficking from cell surface to the Golgi is not yet completed understood. Here we report a mechanism of Golgi translocation of EGFR in which EGF-induced EGFR travels to the Golgi via microtubule (MT)-dependent movement by interacting with dynein and fuses with the Golgi through syntaxin 6 (Syn6)-mediated membrane fusion. We also demonstrate that the Golgi translocation of EGFR is necessary for its consequent nuclear translocation and transcriptional activity. Interestingly, foreign protein such as bacterial cholera toxin, which is known to activate its pathological function through the Golgi/ER retrograde pathway, also utilizes the MT/Syn6 pathway. Thus, the MT, and syntaxin 6 mediated trafficking pathway from cell surface to the Golgi and ER defines a comprehensive retrograde trafficking route for both cellular and foreign molecules to travel from cell surface to the Golgi and the nucleus.