Phospholipase D promotes Arcanobacterium haemolyticum adhesion via lipid raft remodeling and host cell death following bacterial invasion

<p>Abstract</p> <p>Background</p> <p><it>Arcanobacterium haemolyticum </it>is an emerging bacterial pathogen, causing pharyngitis and more invasive infections. This organism expresses an unusual phospholipase D (PLD), which we propose promotes bacterial pathogenesis through its action on host cell membranes. The <it>pld </it>gene is found on a genomic region of reduced %G + C, suggesting recent horizontal acquisition.</p> <p>Results</p> <p>Recombinant PLD rearranged HeLa cell lipid rafts in a dose-dependent manner and this was inhibited by cholesterol sequestration. PLD also promoted host cell adhesion, as a <it>pld </it>mutant had a 60.3% reduction in its ability to adhere to HeLa cells as compared to the wild type. Conversely, the <it>pld </it>mutant appeared to invade HeLa cells approximately two-fold more efficiently as the wild type. This finding was attributable to a significant loss of host cell viability following secretion of PLD from intracellular bacteria. As determined by viability assay, only 15.6% and 82.3% of HeLa cells remained viable following invasion by the wild type or <it>pld </it>mutant, respectively, as compared to untreated HeLa cells. Transmission electron microscopy of HeLa cells inoculated with <it>A. haemolyticum </it>strains revealed that the <it>pld </it>mutant was contained within intracellular vacuoles, as compared to the wild type, which escaped the vacuole. Wild type-infected HeLa cells also displayed the hallmarks of necrosis. Similarly inoculated HeLa cells displayed no signs of apoptosis, as measured by induction of caspase 3/7, 8 or 9 activities.</p> <p>Conclusions</p> <p>These data indicate that PLD enhances bacterial adhesion and promotes host cell necrosis following invasion, and therefore, may be important in the disease pathogenesis of <it>A. haemolyticum </it>infections.</p

Vastasyntyneiden GBS-taudin ehkäisy – asiantuntijaryhmän suositus

B-ryhmän beetahemolyyttinen streptokokki (GBS) on vastasyntyneiden yleisin bakteremian ja meningiitin aiheuttaja. Suuri osa vastasyntyneiden varhaisista GBS-infektioista voidaan ehkäistä antamalla synnytyksenaikainen mikrobilääkeprofylaksi loppuraskauden GBS-seulonnassa positiiviseksi osoitetuille synnyttäjille. Jos GBS-seulontaviljelyä ei ole tehty, infektioriski arvioidaan synnytyksen käynnistymisen yhteydessä

Invasive Group B Streptococcal Infections in Finland: A Population-based Study

We analyzed surveillance data on group B streptococcus (GBS) infection in Finland from 1995 to 2000 and reviewed neonatal cases of early-onset GBS infection in selected hospitals in 1999 to 2000. From 1995 to 2000, 853 cases were reported (annual incidence 2.2–3.0/100,000 population). We found 32–38 neonatal cases of early-onset GBS disease per year (annual incidence 0.6–0.7/1,000 live births). In five hospitals, 35% of 26 neonatal cases of early-onset GBS infection had at least one risk factor: prolonged rupture of membranes, preterm delivery, or intrapartum fever. Five of eight mothers screened for GBS were colonized. In one case, disease developed despite intrapartum chemoprophylaxis. Although the incidence of early-onset GBS disease in Finland is relatively low, some geographic variation exists, and current prevention practices are suboptimal. Establishing national guidelines to prevent perinatal GBS is likely to reduce the incidence of the disease

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Evaluation of the Oricult-N Dipslide for Laboratory Diagnosis of Vaginal Candidiasis

The Oricult-N semiquantitative dipslide (Orion Diagnostica, Espoo, Finland) was evaluated for the laboratory diagnosis of vaginal candidiasis. It was compared with broth culture (Vagicult; Orion Diagnostica). Oricult-N was positive for 14.5% of 124 symptomatic patients and 12% of 50 asymptomatic controls. The results for broth cultures were 17 and 22%, respectively. Thus, the test group and the control group did not differ significantly by either method. High vaginal yeast counts (≥10(5) CFU/ml) were detected by Oricult-N in 7% of patients and in 0% of controls, but both groups harbored low numbers of yeasts. An accurate quantitative cutoff point separating a level of yeast associated with infection from vaginal yeast carriage could not be defined in the study. Nevertheless, the easy semiquantitation allowed by the Oricult-N method could be helpful because, especially in low-count carriers of Candida, other potential causes of vaginal symptoms should be considered. The Oricult-N method was technically simple and could be applied in primary health care. Further studies are required, however, before Oricult-N can be recommended as a routine diagnostic tool

Geant4 Monte Carlo simulations of the galactic cosmic ray radiation environment on-board the international space station/columbus

A characterization of the Galactic Cosmic Ray (GCR) induced radiation environment on-board Columbus and the Inter-national Space Station (ISS) has been carried out using the Geant4 Monte Carlo particle transport toolkit and detailed geometry models of Columbus and ISS. Dose and dose equivalent rates, as well as penetrating particle spectra are presented. Simulation results indicate that the major part of the dose rates due to GCR protons are associated with secondary particles produced in the hull of ISS. Neutrons contribute about 15% of the GCR proton dose equivalent rate and mesons about 10%. More than 40% of the simulated GCR proton dose and dose equivalent rates are due to protons in the energy range above 10 GeV. Protons in the energy range above 50 GeV contribute only 5% to the dose rates. The total simulated dose and dose equivalent rates at solar maximum are 63 mu Gy/d and 123 mu Sv/d, respectively. The dose equivalent rate underestimates measurements made during the 2001 solar maximum. The discrepancy can be attributed to deficiencies in hadronic ion-nuclei interaction models for heavy ions and to the lack of such models above 10 GeV/N in Geant4