WELCOME TO THE CENTER FOR INFECTION & IMMUNITY OF LILLE

Our projects are focused on two major bacterial respiratory pathogens: Mycobacteria and Bordetella.

Today, respiratory infections, many of which are caused by pathogenic bacteria, are among the world’s most successful killers.

Tuberculosis (TB) is the cause of approximately 1.8 million annual deaths. Pertussis, the existence of which had almost been forgotten, shows a dramatic global re-emergence, including in high-vaccine coverage countries.

The choice of working in parallel on these two bacterial models is motivated by the fact that whereas both bacteria infect the human respiratory tract, they follow extremely different strategies that we believe are interesting to compare. For both infections, vaccines are available but the re-emergence of both diseases indicates that there is a need for improvement. Moreover, while antibiotic resistance of B. pertussis is currently not a concern, the global spread of multidrug resistant TB is a major problem.

The objectives of the team are :

(i) to study the molecular mechanisms of pathogenicity of B. pertussis and M. tuberculosis pathogen families,

(ii) to analyse the genome evolution of M. tuberculosis and the genetic regulation of the two pathogens,

(iii) to use this knowledge to develop novel approaches to design better vaccines, new therapeutics and new methods for molecular diagnostics and molecular surveillance, which are urgently needed to fight against these deadly scourges.

Thus, our research is a continuum from a continuous acquisition of basic knowledge to the development of clinical applications and investigations. These ambitious objectives are led with the help of collaborations with many academic French collaborators, including within the CIIL, and international laboratories, in the framework of multiple ANR and EU programmes, and with very active private partners participating to the clinical and industrial development of our discoveries.

Deciphering the Protein-Protein Interactions (PPI) in pathogenic bacteria may help to understand the physiology of the cell and to elucidate host-pathogen interactions, in which proteins play crucial roles. In addition, the study of PPI may facilitate the discovery of protein functions by the ‘guilty by association’ principle.

As PPI are key factors in Mycobacterium tuberculosis physiology and virulence, we are particularly interested in deciphering PPI network in mycobacteria at the cell wall and the membrane level. For example, mycolic acid biosynthesis, which is the target several antiTB drugs, relies on specialized and interconnected protein complexes. Hence, the identification and the characterization of PPI may represent an attractive approach for the development of new drugs and/or peptidomimetics. In addition, deciphering the PPI network of M. tuberculosis will lead to the identification of critical steps required for mycobacterial infection and will allow a better understanding of TB pathogenesis. (contact: romain.veyron-churletibl.cnrsfr)

The Bordetellae, encompassing the human pathogen B. pertussis and the veterinary pathogen B. bronchiseptica, produce an arsenal of virulence factors such as adhesins and toxins, that allow the bacteria to transmit, infect and colonize the respiratory tract of the host. These bacteria regulate their virulence factor expressions according to environmental conditions. Hence, these species have a complementary set of capabilities that is regulated in an inverse fashion. In the virulence phase the virulence-activated genes or vags are transcribed and their expression is regulated by a two-component system BvgAS. In the a-virulence phase, the vags are not expressed but instead, the virulence-repressed genes or vrgs are expressed. The expression of the vrgs is regulated by another two-component system RisA/K and by the action of BvgR, a c-di-GMP phosphodiesterase. Using molecular biology and omics’s technologies, our goal is to define the regulation network and the mode of regulation involving the BvgASR and the RisAK systems. Additionally, B. pertussis encodes for up to 16 different two-component systems arguing on the extreme complexity of the Bordetella gene expression biology. (contact: loic.coutteinsermfr)

Our team coordinates the “Mustart” project recently funded by the French initiative “Investments for the Future”(PIA3). Mustart associates 9 French academic experts to develop multifaceted regimens targeting the most coriaceous TB bacilli in their peculiar physiological niches, and to identify biomarkers of the treatment progress. (Contact: alain.baulardinsermfr )