Team Camille LOCHT

Bacterial respiratory infections : Pertussis and Tuberculosis

The research activity is focused on the molecular pathogenesis of bacterial respiratory infections, especially pertussis and tuberculosis. Today, respiratory infections, many of which are caused by pathogenic bacteria, are still among the world’s most successful killers. Tuberculosis (TB) is the cause of approximately 1.5 million annual deaths. Other respiratory diseases, such as pertussis, the existence of which had almost been forgotten, show a dramatic re-emergence at a global level, including in European countries with wide vaccine coverage. The objectives of the team is (i) to study the molecular details of the pathogenic mechanisms of Bordetella pertussis and Mycobacterium tuberculosis and (ii) to try to use this knowledge to develop novel approaches to design better vaccines, new therapeutic molecules and new diagnostic or molecular typing methods, in other words, to help solve unsolved problems with pertussis and TB. Our research represents a continuum from very basic aspects all the way to applications and clinical investigations, with the help of collaborations with other French (within and outside of the Center for Infection and Immunity of Lille) and foreign laboratories, including collaborators in the framework of the programmes of the European Union, in which we participate very actively.

The choice of the two bacterial models is motivated by the fact that both infect the respiratory tract of man, but one is very pathogenic (virtually every immunologically naive individual infected with B. pertussis will develop pertussis within weeks following the infection), while the other is very poorly pathogenic (only approximately 5 to 10% of the M. tuberculosis-infected individuals will develop active TB during their lifetime). On the other hand, M. tuberculosis is much more successful than B. pertussis, as approximately 1/3 of the world population is infected with the tubercle bacillus. B. pertussis is essentially, but not exclusively, an extracellular pathogen, while M. tuberculosis is essentially, but not exclusively, an intracellular pathogen. For both infections vaccines are available, but the re-emergence of both diseases indicates that these vaccines will have to be improved. Nevertheless, the availability of protective vaccines provides us with tools that will allow us to study the mechanisms of protective immunity.

Since the pathogenic potential of a virulent bacterium largely depends on its interaction with the host, it involves essentially factors that are either secreted by the pathogen or that are displayed at its surface. The study of the bacterial envelope constitutes therefore our first research theme. Many genes involved in virulence are regulated in response to environmental conditions. The study on the regulation of the production of the virulence factors constitutes thus our second research theme. Finally, the third theme concerns more specifically research applied to the development of new vaccines. In that context we wish to fully integrate all the knowledge obtained in themes 1 and 2 to develop novel vaccine approaches against pertussis and TB.

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