Sciences biomédicales - Transcriptional regulators of development in free living and obligate intra-cellular alpha-proteobacteria

Alpha-proteobacteria subdivision is a very heterogeneous group of Gram-negative bacteria with very different life styles: Intracellular pathogens for animals (Brucella, Rickettsia) or plants (Agrobacteria), plant endosymbionts (Rhizobia), photosynthetic bacteria (Rhodobacter) or even free-living bacteria (Caulobacter). Together with this diversity of life forms and ecological niches colonized, the alpha-proteobacteria class is also one of the bacterial groups in which cell cycle regulation has been studied in more details. One of its members, Caulobacter crescentus (Cc), has become a model organism to study the primordial bacterial cell cycle. In addition, and while many bacteria divide by symmetric binary fission, many alpha-proteobacteria have strikingly asymmetric cell cycles, each round of division producing two different daughter cells that differs significantly in their morphology and reproductive state. To establish this asymmetry, these species employ a complex cell cycle regulatory pathway controlled by CtrA, a signature protein of the alpha-proteobacteria. CtrA is an essential DNA-binding response regulator which acts as a transcription factor controlling numerous genes with cell cycle-relevant functions as well as a regulator of chromosome replication. Although CtrA network has been well studied for many subgroups of the alpha-proteobacteria class, Rickettsiales order that encompass numerous intracellular pathogens remains an uncharted territory.

The first aim of my PhD project is to characterize the function of CtrA of Orientia tsutsugamushi (Ot), an obligate intracellular pathogen (Rickettsiales Pathogen classified as P3) responsible for a disease called scrub typhus in humans. The second part of the project focuses on characterization of TrcR of Ot, also a signature protein of the alpha-proteobacteria. TrcR was recently identified in the laboratory and characterized to associate and to track with the RNA polymerase to promote transcription and protect against antibiotics (quinolones).