Biology of Spirochetes


  HEADDr PICARDEAU Mathieu / mpicard@pasteur.fr
  MEMBERSBOURGUIGNON Claudia / Dr BOURHY Pascale / Dr CORNET Murielle / Dr FERQUEL Elisabeth / LOUVEL Hélène / RISTOW Paula


  Annual Report

Spirochetes are the causative agents of several important animal and human diseases such as Lyme disease and leptospirosis. The unit is composed of a research group on Leptospira and the National Reference Centers for Borrelia and Leptospira (also WHO collaborating Center for Leptospira).

In 2006, the main research activities included:

i) Comparative genomics between saprophytic and pathogenic Leptospira

In collaboration with the Genomic Platform of the Pasteur Institute, we sequenced the genome of the saprophyte Leptospira biflexa which is our model bacteria. Indeed, numerous tools for genetic manipulation of this saprophytic strain have been developed by our group in the recent years, including random and targeted mutagenesis. We have started the comparison of the genetic content between L. biflexa and pathogenic species that have been already sequenced. Comparative genomics should reveal clues on the life-styles of Leptospira in the environment and in the infected host.

ii) Iron acquisition and regulation in Leptospira

Using both targeted and random mutagenesis in L. biflexa, we characterized iron acquisition systems such as TonB-dependent receptors and an ABC transporter. We also identified a two-component system involved in heme metabolism. Our results show that Leptospira have evolved various strategies for fulfilling their iron requirements. Further studies will include characterization of the mechanisms involved in metabolic responses to iron availability.

iii) Identification of virulence factors in Leptospira

The main objective of the unit is the study of virulence factors in pathogenic strains of Leptospira and the identification of vaccine candidates. We have demonstrated gene transfer for pathogenic strains of Leptospira using transposition of a transposon of eukaryotic origin. One of the first transposon mutants characterized was a mutant with an insertion into a putative gene encoding an OmpA-domain containing protein. Our preliminary results show that this mutant is avirulent in guinea pigs, whereas the wild-type and the complemented strains are virulent. We are currently testing other genes that could be involved in one or several steps of the infectious process.

iv) Diagnosis and epidemiology of Leptospira and Borrelia

The main objective of the National Reference Centers is to transmit, each year, the epidemiological traits of Leptospirosis and Lyme disease to Health authorities. We also have the duty to improve diagnostic techniques. For example, we developed a rapid and simple typing method based on the analysis of the polymorphism of variable-number tandem repeats (VNTR) loci in the genome of the pathogenic species of Leptospira.

picardeau.jpg

Microscopie électronique de L. biflexa

Electronic microscopy of L. biflexa



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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