European Initiative for basic research in Microbiology and Infectious Diseases
Industry-Academia Partnerships and Pathways
European Initiative for basic research in Microbiology and Infectious Diseases
Industry-Academia Partnerships and Pathways
The seconded and recruited researchers are working on three Work Packages (WP), as detailed below:
WP1 Virulence proteins of enteric bacteria in the gut lumen and epithelium 
WP1 Virulence proteins of enteric bacteria in the gut lumen and epitheliumAnaerobiosis and gene regulation (start 1/11/2009)
The Shigella lipoprotein export protein, Lol, is down-regulated under anaerobic conditions. Lol is involved in transport of lipoproteins required for the Type Three Secretion System (TTSS), an essential virulence factor (Francesco Berlanda Scorza, seconded from Novartis to Imperial College London).
RNA-sequencing (RNA-seq) experiments in the presence and absence of oxygen are underway to identify further genes regulated by oxygen (Marta Vergara Irigaray, recruited by Imperial College London).
In addition, an improved purification protocol for the native TTSS has been developed and structural characterization has been initiated (Anastasia Gazi, recruited by Institut Pasteur)
Adhesion in mucosal pathogens (Start 1/6/2010)
Interactions between adhesive pilin proteins PilM, PilN, PilO and PilP of meningococcus have been characterized after immunoprecipitation. The 4 proteins form a complex in the inner membrane in the absence of other pilins. A manuscript is in preparation (Marta Castagnini, seconded from Novartis to Imperial College London).
Manipulation of the host adaptive immune response by Shigella (Start 15/04/2009)
In the final months of the secondment of E. Frigimelica, several control experiments were performed in response to reviewers comments to a manuscript entitled “The Shigella flexneri Type Three Secretion System effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism”. The manuscript was subsequently accepted for publication. In addition, it was found out that the “in vitro” infection of Jurkat cells by Shigella impairs the formation of the immune synapse (Elisabetta Frigimelica, seconded from Novartis to Institut Pasteur).
Mechanisms of regulation of GNA2132 in Neisseria meningitdis (Start 3/05/2010)
Using transcriptome analysis, progress has been made in understanding the role of glucose and lactose in regulation of components of an experimental vaccine against meningococcal meningitis. In addition, progress has also been made in understanding the role of the contact regulatory element of Neisseria, CREN, in regulation of expression of GNA2132 and other virulence factors (Ana Sofia Maceira Antunes, seconded from Institut Pasteur to Novartis).
WP2 Creation of a pilus or pilus subunits based vaccine against S. pneumoniae (Start 1/7/2009) WP2 Creation of a pilus or pilus subunits based vaccine against S. pneumoniae (Start 1/7/2009)The interaction of the S. pneumoniae pilus adhesin RrgA with macrophages has been further characterized using fluorescent microspheres conjugated with recombinant RrgA. The data indicate that the RrgA adhesin directly promotes phagocytosis (Tiziana Spadafina, seconded from Novartis to Karolinska Institutet).
S. pneumoniae produces high levels of hydrogen peroxide by converting pyruvate to acetyl phosphate and hydrogen peroxide via a pyruvate oxidase encoded by the spxB gene. Natural and recombinant spxB mutants showed decreased binding ability and were less internalized by phagocytic cells compared to wild type strains. The results suggest that spxB mutants are selected in vivo because they are more resistant to clearance by host macrophages. The findings establish a crucial role of spxB mutations in the phagocytosis (Marilena Gallotta, seconded from Novartis to Karolinska Institutet).
WP3 Vaccination against Helicobacter pylori and exploration of determinants of immune protection (Start 1/1/2010) WP3 WP3 Vaccination against Helicobacter pylori and exploration of determinants of immune protection (Start 1/1/2010)H. pylori permanently modifies gene expression in host cells during infection. Bacterial produced γ-glutamyltransferase (GGT) was identified as the main virulence factor that induces transcription of SIRT1, a histone deacetylase which also has important non-histone targets, including P53, and this induction is dependent on GGT enzymatic activity (Matteo Metruccio, seconded from Novartis to Max Planck Institute for Infection Biology).
Next generation sequencing is now being used to analyze the regulation of host gene expression after H. pylori infection (Fernando Garcia Alcalde, recruited at Max Planck Institute for Infection Biology).
A second approach is studying the induction of anti-mcrobial peptides in human H. pylori infected dendritic and T-cells. Preliminary data show robust anti-H.pylori responses (Paolo Montanari, seconded from Novartis to Max Planck Institute for Infection Biology).