A Modular BAM Complex in the Outer Membrane of the α-Proteobacterium Caulobacter crescentus

Mitochondria are organelles derived from an intracellular α-proteobacterium. The biogenesis of mitochondria relies on the assembly of β-barrel proteins into the mitochondrial outer membrane, a process inherited from the bacterial ancestor. Caulobacter crescentus is an α-proteobacterium, and the BAM (β-barrel assembly machinery) complex was purified and characterized from this model organism. Like the mitochondrial sorting and assembly machinery complex, we find the BAM complex to be modular in nature. A ∼150 kDa core BAM complex containing BamA, BamB, BamD, and BamE associates with additional modules in the outer membrane. One of these modules, Pal, is a lipoprotein that provides a means for anchorage to the peptidoglycan layer of the cell wall. We suggest the modular design of the BAM complex facilitates access to substrates from the protein translocase in the inner membrane

Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial

International audienceBackground : Inappropriate fluid therapy during surgery is associated with significant morbidity and mortality. Fewstudies have examined the effects of particular types of fluids (crystalloid or colloid solutions) in surgical patients,especially with the goal of hemodynamic optimization. Isotonic saline is the most commonly used fluid worldwidebut may be associated with potential nephrotoxicity. Hydroxyethyl starch (HES) solutions are widely used in surgicalpatients as a component of goal-directed fluid optimization strategies, but several large multicenter studies havesuggested increased rates of acute kidney injury and adverse events with the use of HES in ICU patients. Despitewhat may be inferred from physiological studies, the benefit and harm of 0.9 % saline and HES during hemodynamictherapy have not been clearly established in surgical patients.Methods/Design : The FLASH trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded,two-arm trial, randomizing 826 patients with moderate-to-high risk of postoperative complications to receive 6 % HES130/0.4 or 0.9 % saline during individualized goal-directed fluid optimization. The primary outcome measure is acomposite of death or major postoperative complications within 14 days following surgery.Thesamplesizewillallowthedetectionofa10%absolutebetween-groupdifferenceintheprimaryoutcomemeasurewith a type 1 error rate of 5 % and power of 95 %, assuming a 5% mortality rate and 20 % morbidity (thus 25 % for thecomposite endpoint).Discussion : The FLASH trial may provide important data on the efficacy and safety of commonly used fluid solutions andcould have a significant impact on future treatment of surgical patients.Trial registration : ClinicalTrials.gov Identifier: NCT02502773. Registered 16 June 2015

Additional file 1: of Fluid loading in abdominal surgery - saline versus hydroxyethyl starch (FLASH Trial): study protocol for a randomized controlled trial

Acute kidney injury (AKI) risk index. (PDF 50 kb

Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli

Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin ?. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin ? and meprin ?. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization