Bacterial Molecular Genetics  

  HEADProf. COLE Stewart (until May 31, 2007) Dr. BROSCH Roland ( per interim June 1 – December 31, 2007) /
  MEMBERSANTUNES Ana Sofia, Dr. BRODIN Priscille, Dr. BOTTAI Daria, Dr. BOULKROUN Sheerazed, CALEECHURN Laxmee, Emilie CAMIADE, Dr. DEMANGEL Caroline, Dr. DUPUY Bruno, Anne-Marie FARGUES
Wafa FRIGUI, Dr. GARNIER Thierry, Dr. HONORE Nadine, Dr. KANDASAMY Revathi, MONOT Marc, SAINT-JOANIS Brigitte, Dr. SALA Claudia

  Annual Report

The Bacterial Molecular Genetics unit is world-renowned for its achievements in the fields of mycobacterial and clostridial research, in particular for its pioneering work on the molecular basis of multidrug-resistant tuberculosis, and the genomics and evolutionary biology of Mycobacterium tuberculosis and Mycobacterium leprae. Our publications from this period are amongst the most highly cited in the field of microbiology. In 2007 the unit was working on three broad themes: the functional genomics of tuberculosis, drug discovery and vaccine development; the pathogenesis of Buruli ulcer and leprosy; and control of toxigenesis in Clostridium difficile. There was extensive interaction between the groups and much sharing of expertise and resources. We greatly benefited from intramural collaborations with structural biologists, biochemists and immunologists, as well as numerous national and international partnerships.

Among the hypothesis-driven research topics are structure-function studies of a novel protein secretion apparatus, ESX-1, and its contribution to the pathogenicity of M. tuberculosis, and the genomic analyses and comparison of attenuated mycobacterial strains such as BCG and M. tuberculosis

Buruli ulcer research is focused on understanding the cytotoxic effects of the macrolide toxin, mycolactone, and its suppression of cellular immune responses through disruption of signal transduction pathways. The natural history and ecology of Buruli ulcer, including the role of insects as potential vectors, are being studied. In 2007, our leprosy research involved the development of tools for early diagnosis and epidemiology.

Clostridium difficile is an emerging pathogen and a leading source of often-lethal nosocomial infections. Toxin production is at the heart of its pathogenicity and its regulation has been the subject of intense research. An ECF sigma factor has been identified as a pivotal regulator and its interplay with environmental sensors is being unravelled.

Keywords: Tuberculosis, mycobacteria, Clostridium, genomics, pathogenesis


Brosch, R., Gordon, S.V., Garnier, T., Eiglmeier, K., Frigui, W., Valenti, P., Dos Santos, S., Duthoy, S., Lacroix, C., Garcia-Pelayo, C., Inwald, J.K., Golby, P., Nunez Garcia, J., Hewinson, R.G., Behr, M.A., Quail, M.A., Churcher, C., Barrell, B.G., Parkhill, J., and Cole, S.T. (2007) Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A. 104: 5596-5601.

Coutanceau, E., Decalf, J., Martino, A., Babon, A., Winter, N., Cole, S.T., Albert, M.L., and Demangel, C.(2007) Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. J Exp Med. 2007 Jun 11;204(6):1395-403

Matamouros, S., England, P., and Dupuy, B. (2007) Clostridium difficile toxin expression is inhibited by the novel regulator TcdC. Mol Microbiol. 64:1274-88.

Monot, M., Honore, N., Garnier, T., Araoz, R., Coppee, J. Y., Lacroix, C., Sow, S., Spencer, J. S., Truman, R. W, Williams, D. L., Gelber, R., Virmond, M., Flageul, B., Cho, S. N., Ji, B., Paniz-Mondolfi, A., Convit, J., Young, S., Fine, P.E., Rasolofo, V., Brennan, P. J., and Cole, S. T. (2005) On the origin of leprosy. Science. 308:1040-2.

Stinear, T.P., Mve-Obiang, A., Small, P.L.C., Frigui, W., Pryor, M.J., Brosch, R., Jenkin, G.A., Johnson, P.D.R, Davies, J.K., Lee, R.E., Adusumilli, S., Garnier, T., Haydock, S.F., Leadlay, P.F., and Cole, S.T. (2004) Giant plasmid-encoded polyketide synthases produce the macrolide toxin of Mycobacterium ulcerans. Proc Natl Acad Sci U S A. 101: 1345-1349

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Activity Reports 2007 - Institut Pasteur
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