The bacterial type VI secretion system (T6SS) is a macromolecular machine that injects effectors into prokaryotic and eukaryotic cells. The mode of action of the T6SS is similar to contractile phages: the contraction of a sheath structure pushes a tube topped by a spike into target cells. Effectors are loaded onto the spike or confined into the tube. In enteroaggregative Escherichia coli, the Tle1 phospholipase binds the C-terminal extension of the VgrG trimeric spike. Here, we purify the VgrG-Tle1 complex and show that a VgrG trimer binds three Tle1 monomers and inhibits their activity. Using covalent cross-linking coupled to high-resolution mass spectrometry, we provide information on the sites of contact and further identify the requirement for a Tle1 N-terminal secretion sequence in complex formation. Finally, we report the 2.6-A-resolution cryo-electron microscopy tri-dimensional structure of the (VgrG)(3) -(Tle1)(3) complex revealing how the effector binds its cargo, and how VgrG inhibits Tle1 phospholipase activity. The inhibition of Tle1 phospholipase activity once bound to VgrG suggests that Tle1 dissociation from VgrG is required upon delivery.
Title: [Prescription of cholinesterase inhibitors in Alzheimer's disease in France in 2000-2001: an assessment of compliance with national guidelines for diagnosis and follow-up] Dartigues JF, Douet C, Rey M, Sencey M, Pigeon M, Sardin F, Maugendre P, Crochet B Ref: Rev Neurol (Paris), 161:957, 2005 : PubMed
INTRODUCTION: Alzheimer's disease (AD) became a treatable disease about ten years ago when cholinesterase inhibitors (CI) became available. We conducted a national population-based study in France in order to describe patients taking CI in 2001, to compare the diagnostic procedures of AD and the drug prescriptions with the French National guidelines, and to analyze the follow-up procedures of the patients. METHODS: The study was carried out in nine regions of France between December 1st 2000 and February 28th 2001 and included 3510 patients with CI treatment prescribed by the physicians affiliated with the National Social Security Health Care Fund. RESULTS: We found that the diagnostic procedures and the prescriptions were in compliance with the national guidelines with more than 90 percent of patients referred to a specialist, brain imaging in 85 percent and a MMSE scored between 10 and 26 in more than 90 percent. However, patient follow-up was in compliance with the guidelines in only 50 percent of patients. CONCLUSION: Diagnostic procedures of AD and first prescription of CI seem to be adequate in France, but patient follow-up needs to be improved.
Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.
