Comparative Pathogenomics of Escherichia coli: Polyvalent Vaccine Target Identification through Virulome Analysis.

Comparative genomics of bacterial pathogens has been useful for revealing potential virulence factors. Escherichia coli is a significant cause of human morbidity and mortality worldwide but can also exist as a commensal in the human gastrointestinal tract. With many sequenced genomes, it has served as a model organism for comparative genomic studies to understand the link between genetic content and potential for virulence. To date, however, no comprehensive analysis of its complete "virulome" has been performed for the purpose of identifying universal or pathotype-specific targets for vaccine development. Here, we describe the construction of a pathotype database of 107 well-characterized completely sequenced pathogenic and nonpathogenic E. coli strains, which we annotated for major virulence factors (VFs). The data are cross referenced for patterns against pathotype, phylogroup, and sequence type, and the results were verified against all 1,348 complete E. coli chromosomes in the NCBI RefSeq database. Our results demonstrate that phylogroup drives many of the "pathotype-associated" VFs, and ExPEC-associated VFs are found predominantly within the B2/D/F/G phylogenetic clade, suggesting that these phylogroups are better adapted to infect human hosts. Finally, we used this information to propose polyvalent vaccine targets with specificity toward extraintestinal strains, targeting key invasive strategies, including immune evasion (group 2 capsule), iron acquisition (FyuA, IutA, and Sit), adherence (SinH, Afa, Pap, Sfa, and Iha), and toxins (Usp, Sat, Vat, Cdt, Cnf1, and HlyA). While many of these targets have been proposed before, this work is the first to examine their pathotype and phylogroup distribution and how they may be targeted together to prevent disease.

Economic crisis, health systems and health in Europe: Impact and implications for policy

The crisis has given substance to an old and often hypothetical debate about the financial sustainability of health systems in Europe. For years it was the spectre of ageing populations, cost-increasing developments in technology and changing public expectations that haunted European policy-makers troubled by growth in health sector spending levels. The real threat, however, came in the shape of a different triumvirate: financial crisis, sovereign debt crisis and economic crisis. After 2008 the focus of concern turned from the future to the present, from worrying about how to pay for health care in thirty years' time to how to pay for it in the next three months. Not all European countries were affected by the crisis. Among those that were, the degree to which the health budget suffered varied. Some countries experienced substantial and sustained falls in public spending on health; others did not. These changes and comparative differences provide a unique opportunity to observe how policy-makers respond to the challenge of meeting health care needs when money is even tighter than usual. The magnitude of the crisis ­ its size, duration and geographical spread ­ makes the endeavour all the more relevant. We know from the experience of previous crises that economic shocks pose a threat to health and health system performance. They increase people's need for health care and make it more difficult for them to access the care they need. They affect health systems by heightening fiscal pressure, stretching government resources at the same time as people rely more heavily on publicly financed health services. We also know that negative effects on health tend to be concentrated among specific groups of people ­ especially those who experience unemployment ­ and that they can be mitigated by public policy action. While many important policy levers lie outside the health sector, in the hands of those responsible for fiscal policy and social protection, the health system response is nonetheless critical.

Iron acquisition and transport in Staphylococcus aureus.

Pathogenic Gram-positive bacteria encounter many obstacles in route to successful invasion and subversion of a mammalian host. As such, bacterial species have evolved clever ways to prevent the host from clearing an infection, including the production of specialized virulence systems aimed at counteracting host defenses or providing protection from host immune mechanisms. Positioned at the interface of bacteria/host interactions is the bacterial cell wall, a dynamic surface organelle that serves a multitude of functions, ranging from physiologic processes such as structural scaffold and barrier to osmotic lysis to pathogenic properties, for example the deposition of surface molecules and the secretion of cytotoxins. In order to succeed in a battle with host defenses, invading bacteria need to acquire the nutrient iron, which is sequestered within host tissues. A cell-wall based iron acquisition and import pathway was uncovered in Staphylococcus aureus. This pathway, termed the isd or iron-responsive surface determinant locus, consists of a membrane transporter, cell wall anchored heme-binding proteins, heme/haptoglobin receptors, two heme oxygenases, and sortase B, a transpeptidase that anchors substrate proteins to the cell wall. Identification of the isd pathway provides an additional function to the already bountiful roles the cell wall plays in bacterial pathogenesis and provides new avenues for therapeutics to combat the rise of antimicrobial resistance in S. aureus. This review focuses on the molecular attributes of this locus, with emphasis placed on the mechanism of iron transport and the role of such a system during infection.