Philippe  GLASER
Biology of Gram-positive Pathogens Unit
Team Bacterial genomics and evolution
Institut Pasteur 25-28 rue du docteur Roux, 75015 Paris
 
Research area of the Unit
 
The general objective of the team is to define the molecular basis of the adaptation of streptococci to their hosts and of their capacity to cause a broad range of diseases by studying their evolution and their population structure at the genome level. Presently we are trying to elucidate the reasons for the emergence of group B streptococcus (GBS) as a major neonatal pathogen in the 60ies, how group A (GAS) and group B streptococci switch from benign colonizers to highly invasive pathogens and how the opportunistic pathogens S. agalactiae and S. gallolyticus adapt to different hosts.
We are characterizing the relative role of point mutations, recombination and exchange of mobile genetic elements (MGEs) in this adaptive process and attempt to determine the functional impact of these genome modifications. We are analyzing both the acquisition and modification of structures and changes in gene expression profiles. MGE are major contributors to the capacity to invade new niches to gain virulence and by these to the emergence of specific lineages. We are studying at the level of the genus streptococcus their diversity, propagation, regulation and the functions they carry.
 
Contribution to the programme
 
Emerging bacterial infections result from genomic modifications leading to new properties enabling a lineage to expand by occupying a new niche or by acquiring new virulence properties. Our contribution to the program is to provide an integrated population genomics approach in order to identify the corresponding genomic modifications and their functional impact and thereby to better understand host-pathogen interaction.
In particular we are interested in addressing the following specific questions:
- Does the genomic structure of human GBS results from and explain the emergence of GBS infections and what are the resulting functional modifications leading to an increased virulence in newborns?
- How do streptococci interact with their mobilome, how do MGEs circulate within the genus at a worldwide level and what is their contribution to the modification of their bacterial host?
- What are the genomic and functional differences between related invasive and carriage GAS and GBS isolates?
Our work is performed in tight collaboration with clinical microbiologists in particular with the National Reference Centre for streptococci and with laboratories from the IP international network.
 
References over the past 5 years
 
1.      Buchrieser, C., Rusniok, C., Garrido, P., Hain, T., ... & Glaser, P., (2011) Complete genome sequence of the animal pathogen Listeria ivanovii, which provides insights into host specificities and evolution of the genus Listeria. J. Bacteriol. 193: 6787-6788.
2.      Da Cunha, V., Guerillot, R., Brochet, M. & Glaser, P., (2011) Integrative and Conjugative Elements Encoding DDE Transposases. In: Bacterial Integrative Mobile Genetic Elements. A. P. Roberts & P. Mullany (eds). Landes Bioscience, pp.
3.      Rusniok, C., Couve, E., Da Cunha, V., El Gana R., ... & Glaser, P., (2010) Genome sequence of Streptococcus gallolyticus: insights into its adaptation to the bovine rumen and its ability to cause endocarditis. J. Bacteriol. 192: 2266-2276.
4.      Brochet, M., Couve, E., Bercion, R., Sire, J. M. & Glaser, P., (2009) Population structure of human isolates of Streptococcus agalactiae from Dakar and Bangui. J. Clin. Microbiol. 47: 800-803.
5.      Brochet, M., Da Cunha, V., Couve, E., Rusniok, C., Trieu-Cuot, P. & Glaser, P., (2009b) Atypical association of DDE transposition with conjugation specifies a new family of mobile elements. Mol. Microbiol. 71: 948-959.
6.      Brochet, M., Rusniok, C., Couve, E., Dramsi, S., Poyart, C., Trieu-Cuot, P., Kunst, F., & Glaser, P., (2008) Shaping a bacterial genome by large chromosomal replacements, the evolutionary history of Streptococcus agalactiae. Proc Natl Acad Sci U S A 105: 15961-15966.
7.      Brochet, M., Couve, E., Zouine, M., Poyart, C. & Glaser, P., (2008) A naturally occurring gene amplification leading to sulfonamide and trimethoprim resistance in Streptococcus agalactiae. J. Bacteriol. 190: 672-680.