Integrative Biology of Emerging Infectious Diseases (IBEID) / Principal investigators
Biology and Genetics of Bacterial Cell Wall Unit
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
Research area of the Unit
Our on-going work and projects for the next following years are aimed at deciphering new knowledge on one of the major “Achilles heals” of bacteria, their cell wall and to improve our future options in dealing with old and “emerging” infectious diseases. Our research can be separated in two complementary subjects: 1) the study of peptidoglycan (PG) metabolism and its role in cell physiology and antibiotic resistance, and 2) the role that cell wall, and in particular, PG metabolism has on host-microbe interactions.
Contribution to the programme
Using Helicobacter pylori as an alternative model system, we have been dissecting the machineries involved in peptidoglycan assembly. For example, we have shown that peptidoglycan elongation by the elongasome can be disrupted by interfering with the stability of the core protein complex PBP2:MreC. Furthermore, we have shown recently that targeting simultaneously PBP2 with a beta-lactam antibiotic, amoxicillin, and another partner of the machinery, Slt, with a natural product, Bulgecin A, leads to a synergistic bacterial killing. This new knowledge can be used to develop multidrug therapies that target at different stages the peptidoglycan biosynthetic pathway reducing potential resistance mechanisms and extending the shelf live of old antibiotics.
References over the past 5 years
1. Bonis, M., A. Williams, S. Guadagnini, C. Wertsand I.G. Boneca. 2012. The effect of bulgecin A on peptidoglycan metabolism and physiology of Helicobacter pylori. Microbial Drug Res. In press.
2. El Ghachi, M. P.-J. Matteï, C. Ecobichon, A. Martins, S. Hoos, C. Schmitt, F. Colland, C. Ebel, M.-C. Prévost, F. Gabel, P. England, A. Dessen & I.G. Boneca. 2011. Characterization of the elongasome core PBP2:MreC complex of Helicobacter pylori. Mol Microbiol. 82. (1):68-86.
3. Bonis, M., C. Ecobichon, S. Guadagnini, M.-C. Prévost & I.G. Boneca. 2010. A M23B-family metallopeptidase of Helicobacter pylori required for cell shape, pole formation and virulence. Mol Microbiol. 78. (4):809-819.
4. Bouskra, D., C. Brézillon, M. Bérard, C. Werst, R. Varona, I.G. Boneca and G. Eberl. 2008. Lymphoid tissue genesis induced by bacterial commensals through NOD1 and β-defensin regulates intestinal homeostasis. Nature. 456. (7221): 507-510.
5. Boneca, I.G., C. Ecobichon, C. Chaput, A. Mathieu, S. Guadagnini, M.-C. Prévost, A. Labigne and H. de Reuse. 2008. Development of inducible systems to engineer conditional mutants of essential genes of Helicobacter pylori. Applied Environm. Microbiol. 74. (7): 2095-2102.
6. Boneca, I.G., O. Dussurget, D. Cabanes, M.-A. Nahori, S. Sousa, M. Lecuit, E. Psylinakis, V. Bouriotis, M. Giovannini, J.P. Hugot, A. Coyle, J. Bertin, A. Namane, J.C. Rousselle, N. Cayet, M.C. Prévost, V. Balloy, M. Chignard, D.J. Philpott, P. Cossart and S.E. Girardin. 2007. A critical role for peptidoglycan N-deacetylationin Listeria evasion from the host innate immune system. Proc Natl Acad Sci U S A. 104. (3): 997-1002.
7. Chaput, C., A. Labigne and I.G. Boneca. 2007. Characterization of Helicobacter pylori lytic transglycosylases. J. Bacteriol. 189. (2): 422-429.