Bacterial pathogens use host as substrates for their proliferation. They thus selected, along evolution, molecular mechanisms allowing them to colonize, feed and proliferate on or inside host organisms. Some bacterial pathogens (like Salmonella or Shigella) are very well characterized, but some bacteria causing worldwide diseases are still poorly understood. It is the case of Brucella, a genus responsible for brucellosis, a major zoonosis affecting many mammals, including domestic animals like sheep, goats and cows. Two research groups are active on Brucella in our research unit.
Brucella belong to the alpha-proteobacteria group, a taxon comprising the bacterial model of differentiation Caulobacter crescentus. C. crescentus is known to be asymmetrically organized at the cellular and molecular levels. In our group, we mainly concentrate our studies on Brucella abortus, a species essentially found in cows infections. We discovered that B. abortus is asymmetrically organized at the molecular level, and we try to evaluate the importance of this asymmetry in simplified models of infection. We also set up molecular tools allowing us to follow the cell cycle progression of B. abortus in culture and inside host cells. We discovered that a large fraction of the bacteria block their DNA replication during the first hours of a cellular infection.
Our current research is an integrated approach to study basic molecular biology of the Brucella abortus pathogen, including :
- enveloppe structure and biosynthesis during polar growth
- DNA replication and repair during agressions in host cells
- feeding and starvation in culture and inside host cells
We use genetic approaches such as deletion strain generation and characterization, genome-wide transposon mutagenesis followed by deep sequencing (Tn-seq), protein binding site identification on Brucella abortus chromosomes (ChIP-seq) and generation of genetically engineered strains to follow protein localization in Brucella abortus.