Molecular recognition of lipopolysaccaride by the lantibiotic nisin

Nisin is a lanthionine antimicrobial effective against diverse Gram-positive bacteria and is used as a food preservative worldwide. Its action is mediated by pyrophosphate recognition of the bacterial cell wall receptors lipid II and undecaprenyl pyrophosphate. Nisin/receptor complexes disrupt cytoplasmic membranes, inhibit cell wall synthesis and dysregulate bacterial cell division. Gram-negative bacteria are much more tolerant to antimicrobials including nisin. In contrast to Gram-positives, Gram-negative bacteria possess an outer membrane, the major constituent of which is lipopolysaccharide (LPS). This contains surface exposed phosphate and pyrophosphate groups and hence can be targeted by nisin. Here we describe the impact of LPS on membrane stability in response to nisin and the molecular interactions occurring between nisin and membrane-embedded LPS from different Gram-negative bacteria. Dye release from liposomes shows enhanced susceptibility to nisin in the presence of LPS, particularly rough LPS chemotypes that lack an O-antigen whereas LPS from microorganisms sharing similar ecological niches with antimicrobial producers provides only modest enhancement. Increased susceptibility was observed with LPS from pathogenic Klebsiella pneumoniae compared to LPS from enteropathogenic Salmonella enterica and gut commensal Escherichia coli. LPS from Brucella melitensis, an intra-cellular pathogen which is adapted to invade professional and non-professional phagocytes, appears to be refractory to nisin. Molecular complex formation between nisin and LPS was studied by solid state MAS NMR and revealed complex formation between nisin and LPS from most organisms investigated except B. melitensis. LPS/nisin complex formation was confirmed in outer membrane extracts from E. coli

Simultaneous endovascular repair of an iatrogenic carotid-jugular fistula and a large iliocaval fistula presenting with multiorgan failure: a case report

<p>Abstract</p> <p>Introduction</p> <p>Iliocaval fistulas can complicate an iliac artery aneurysm. The clinical presentation is classically a triad of hypotension, a pulsatile mass and heart failure. In this instance, following presentation with multiorgan failure, management included the immediate use of an endovascular stent graft on discovery of the fistula.</p> <p>Case presentation</p> <p>A 62-year-old Caucasian man presented to our tertiary hospital for management of iatrogenic trauma due to the insertion of a central venous line into his right common carotid artery, causing transient ischemic attack. Our patient presented to a peripheral hospital with fever, nausea, vomiting, acute renal failure, acute hepatic dysfunction and congestive heart failure. A provisional diagnosis of sepsis of unknown origin was made. There was a 6.5 cm×6.5 cm right iliac artery aneurysm present on a non-contrast computed tomography scan. An unexpected intra-operative diagnosis of an iliocaval fistula was made following the successful angiographic removal of the central line to his right common carotid artery. Closure of the iliocaval fistula and repair of the iliac aneurysm using a three-piece endovascular aortic stent graft was then undertaken as part of the same procedure. This was an unexpected presentation of an iliocaval fistula.</p> <p>Conclusion</p> <p>Our case demonstrates that endovascular repair of a large iliac artery aneurysm associated with a caval fistula is safe and effective and can be performed at the time of the diagnostic angiography. The presentation of an iliocaval fistula in this case was unusual which made the diagnosis difficult and unexpected at the time of surgery. The benefit of immediate repair, despite hemodynamic instability during anesthesia, is clear. Our patient had two coronary angiograms through his right femoral artery decades ago. Unusual iatrogenic causes of iliocaval fistulas secondary to previous coronary angiograms with wire and/or catheter manipulation should be considered in patients such as ours.</p

Bayesian Inference for Structural Vector Autoregressions Identified by Markov-Switching Heteroskedasticity

In this study, Bayesian inference is developed for structural vector autoregressive models in which the structural parameters are identified via Markov-switching heteroskedasticity. In such a model, restrictions that are just-identifying in the homoskedastic case, become over-identifying and can be tested. A set of parametric restrictions is derived under which the structural matrix is globally or partially identified and a Savage-Dickey density ratio is used to assess the validity of the identification conditions. The latter is facilitated by analytical derivations that make the computations fast and numerical standard errors small. As an empirical example, monetary models are compared using heteroskedasticity as an additional device for identification. The empirical results support models with money in the interest rate reaction function.Comment: Keywords: Identification Through Heteroskedasticity, Bayesian Hypotheses Assessment, Markov-switching Models, Mixture Models, Regime Chang