Pathogenesis of Mucosal Bacteria  


  HEADProf. LABIGNE Agnès / alabigne@pasteur.fr
  MEMBERSPermanent: Dr DE REUSE Hilde / Dr GOMPERTS BONECA Ivo / Dr LE BOUGUENEC Chantal / Dr TOUATI Eliette
Temporary: Dr BARRIERE Anne Charlotte / Dr BUSSIERE Françoise, Dr EL GHACHI Meriem, Dr LEDUC Damien / Dr PICHON Christophe and BONIS Mathilde / KAAKOUSH Nadeem / MARTINEZ-JEHANNE Vanessa / MATHIEU Aurélie / ROURE Sophie / SAMPAIO Suely / SCHAUER Kristine / THIBONNIER Marie
Research engineer and technicians: THIBERGE Jean-Michel and du MERLE Laurence / ECOBICHON Chantal / MICHEL Valérie


  Annual Report

The research work of the Unit is focused on the study of human mucosa-associated bacterial pathogens: a) Helicobacter pylori, associated with chronic gastritis, peptic ulcer, and neoplasia, as well as b) pathogenic Escherichia coli.

a) Helicobacter pylori (HP)

Research relates to studies i) on mechanisms by which HPsurvives in extreme acidity, colonizes, persists and causes lesions; ii) on biodiversity of the species; iii) on specific metabolism pathways as a mean to identify new diagnostic or therapeutic target.

Adaptation of HP to the gastric environment and metabolism. Nickel metabolism is unique in HP. NikR, a nickel-responsive regulator, was found to mediate response to acidity and to regulate the expression of a novel mechanism energized by the TonB/ExbB/ExbD machinery to transport nickel across the outer membrane. We also demonstrated that uses a K+ channel as sole uptake system for potassium, a novel feature in the bacterial world.

Studying peptidoglycan (PGN) assembly and its role in host-pathogen interactions. One of the research aspects is to characterize the function of the PGN hydrolases (AmiA, Slt, and MltD) and synthetases (PBP1 and PBP3). How PGN modifications, turnover and recycling vary during the course of natural infections and how this might influence and modulate the host response, are part of the addressed current issues.

Genotoxicity and carcinogenic process associated to HP infection are issues addressed using the big blue mouse mice to analyze the mutagenic effect mainly due to gastric inflammation. HP infection in mice was found to be associated i) with genetic instabilities with a decrease in expression of the mismatch repair system which might play a crucial role in the first steps of the gastric carcinogenic process; ii) with a down regulation of the transcription regulators upstream stimulatory factor USF1 and USF2, members of the cMyc family.

Genetic and biochemical properties of HobA. HobA, the first identified of a new group of initiation factors common to the epsilon proteobacteria, interacts specifically with the oriC-DnaA complex. Depletion of HobA leads to growth arrest and failure to initiate replication.

Comparative genomics. The genome of strain B38, a MALT lymphoma strain, was sequenced. B38 genome is 1 574 080 bp long, encodes 1,495 genes, shares 1403 coding sequences (CDS) with the 3 other HP sequenced genomes (26695, J99 and HPAG1). B38 possesses 45 CDS that are not found in the other genomes.

b) Pathogenic Escherichia coli

Role of bacterial metabolic factors in host colonization. Most E. coli isolates causing renal infections are able to use sugars that are not metabolized by strains of the intestinal tract. Using allelic exchange, several pathways of interest were knocked out to compare in vitro and in vivo the relative fitness of the mutants and of the parental strains by means of competition assays, growth in urine, biofilm formation, as well as colonization of the intestine and the urinary tract of mice.

Participation to the ColiScope project. Annotation and comparative analyses of the genomes of strains belonging to the enteroaggregative pathotype recognized as emerging diarrheal pathogens, are conducted to investigate their pathogenic potential.

Keywords: Helicobacter – gastritis – gastric carcinoma– ulcer – lymphoma – MALT - signalization – acidity – peptidoglycan - mucosa – inflammation –comparative genomics – proteomics – regulation - urease - nickel - adhesion – invasion – metabolom - Escherichia coli

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Injection of radiolabeled peptidoglycan (red/violet staining) into gastric epithelial cells by H. pylori



  Publications

BERNIER-FEBREAU, C., L. du MERLE,E. TURLIN, V. LABAS, J. ORDONEZ, A.-M. GILLES, and C. LE BOUGUENEC.2004. Use of deoxyribose by intestinal and extraintestinal pathogenic Escherichia coli strains: a metabolic adaptation involved in competitiveness. Infect. Immun. 72:6151-6156.

VIALA, J., C. CHAPUT, I.G. BONECA, A. CARDONA, S.E. GIRARDIN, A.P. MORAN, R. ATHMAN, S. MEMET, M.R. HUERRE, A.J. COYLE, P.S. DiSTEFANO, P.J. SANSONETTI, A. LABIGNE, J. BERTIN, D.J. PHILPOTT, R.L. FERRERO. 2004. Nod1 responds to peptidoglycan delivered by the Helicobacter pyloricag pathogenicity island. Nat. Immunol. 5:1166-1174.

STINGL, K.,S. BRANDT, E.-M. UHLEMANN, R. SCHMID, K. ALTENDORF, C.A. ZEILINGER, C.ECOBICHON, A. LABIGNE, E.P. BAKKER, and H. DE REUSE. 2007. Channel-mediated potassium uptake inHelicobacter pyloriis essential for gastric colonization. EMBO J. 26:232-241.

SCHAUER, K.,B. GOUGET, M. CARRIERE, A. LABIGNE, and H. DE REUSE. 2007. Novel nickel transport mechanism across the bacterial outer membrane energized by the TonB/ExbB/ExbD machinery. Mol. Microbiol. 63:1054-1068.

ZAWILAK-PAWLIK, A., A. KOIS, K. STINGL, I.G. BONECA,P. SKROBUK, J. PIOTR, R. LURZ, J. ZAKRZEWSKA-CZERWINSKA, and A. LABIGNE. 2007. HobA - a novel protein involved in initiation of chromosomal replication in Helicobacter pylori.Mol. Microbiol. 65:979-994.





Activity Reports 2007 - Institut Pasteur
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