Role of NleH, a type III secreted effector from attaching and effacing pathogens, in colonization of the bovine, ovine, and murine gut

The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 colonizes human and animal gut via formation of attaching and effacing lesions. EHEC strains use a type III secretion system to translocate a battery of effector proteins into the mammalian host cell, which subvert diverse signal transduction pathways implicated in actin dynamics, phagocytosis, and innate immunity. The genomes of sequenced EHEC O157:H7 strains contain two copies of the effector protein gene nleH, which share 49% sequence similarity with the gene for the Shigella effector OspG, recently implicated in inhibition of migration of the transcriptional regulator NF-kappaB to the nucleus. In this study we investigated the role of NleH during EHEC O157:H7 infection of calves and lambs. We found that while EHEC DeltanleH colonized the bovine gut more efficiently than the wild-type strain, in lambs the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. Using the mouse pathogen Citrobacter rodentium, which shares many virulence factors with EHEC O157:H7, including NleH, we observed that the wild-type strain exhibited a competitive advantage over the mutant during mixed infection. We found no measurable differences in T-cell infiltration or hyperplasia in colons of mice inoculated with the wild-type or the nleH mutant strain. Using NF-kappaB reporter mice carrying a transgene containing a luciferase reporter driven by three NF-kappaB response elements, we found that NleH causes an increase in NF-kappaB activity in the colonic mucosa. Consistent with this, we found that the nleH mutant triggered a significantly lower tumor necrosis factor alpha response than the wild-type strain.

Cross-border Movement of Patients in the EU: A Re-Appraisal

The national welfare state, so it seems, has come under attack by European integration. This article focuses on one facet of the welfare state, that is, health care and on one specific dimension, that is, cross-border movement of patients. The institution which has played a pivotal role in the development of the framework regulating the migration of patients is the European Court of Justice (ECJ). The Court’s activity in this sensitive area has not remained without critics. This was even more so since the Court invoked Treaty (primary) law which not only has made it difficult to overturn case law but also has left the legislator with very little room for manoeuvre in relation to any future (secondary) EU law. What is therefore of special interest in terms of legitimacy is the legal reasoning by which the Court has made its contribution to the development of this framework. This article is a re-appraisal of the legal development in this field.