Research on Mycobacteria and Bordetella
INSERM U1019 – CNRS UMR9017 – Lille University – CHU Lille – Institut Pasteur de Lille
The activities of our team are focused on two bacterial pathogens of the respiratory tract, Mycobacterium tuberculosis and Bordetella pertussis, responsible for tuberculosis and pertussis, respectively. The re-emergence of these two diseases highlights the need for improving existing control tools. Furthermore, the global spread of multidrug-resistant tuberculosis adds to these major public health problems. Our objectives are (i) to study the molecular mechanisms of the pathogenicity of B. pertussis and of M. tuberculosis, (ii) to analyze the genomic evolution of M. tuberculosis and the genetic regulation of the two pathogens, and (iii) to use this knowledge to develop novel approaches for designing better vaccines, improved therapies, diagnostic methods and molecular monitoring, urgently needed to combat these deadly scourges. These ambitious objectives are achieved through collaborations with numerous French and international academic laboratories and with private partners participating in the clinical and industrial development of our discoveries.
- New concept of antibiotic therapy. The studies on the control of transcriptional regulation in M. tuberculosis, in particular on the role of the transcriptional repressors EthR and EthR2 in the bioactivation pathway of ethionamide, made it possible to discover a new class of molecules called “SMARt” and allowing a reversion of resistance in M. tuberculosis to ethionamide, while increasing its antibiotic effect. A phase 1 clinical study has just started in collaboration with GSK and BioVersys.
- Diagnosis of latent tuberculosis. A new diagnostic test for latent tuberculosis, based on the HBHA adhesin discovered and studied in the laboratory, is currently in development in partnership with Lionex and the Université Libre de Bruxelles.
- New molecular diagnostic and surveillance tests for multidrug-resistant tuberculosis and leprosy. Research on the genomics and evolution of M. tuberculosis has enabled the creation of diagnostic tests based on next generation sequencing (NGS) by Genoscreen in collaboration with our laboratory. These tests, one of which is already used by WHO for monitoring multidrug resistance, are being clinically evaluated in two H2020 projects involving European and African partners.
- New vaccines against pertussis and other diseases. The studies on B. pertussis virulence factors and bacterial pathogenesis have made it possible to construct a genetically attenuated strain (BPZE1) capable of mimicking a natural infection without inducing pathology. A license and collaboration agreement with ILIAD Biotechnologies now allows the further development of this vaccine, which is currently in clinical phase 2 in the United States. The use of BPZE1 as an anti-inflammatory agent and as a recombinant nasal vaccine against various diseases, including Covid-19, is being investigated with funding from the Ministry of Research.
ERA4TB (European Regimen Accelerator for Tuberculosis) is an international consortium aiming to accelerate the development of new treatment regimens for tuberculosis.
Tuberculosis is the leading cause of death from infectious disease worldwide, and the continued development of antibiotic resistance makes the disease very difficult to treat. ERA4TB is a public-private partnership designed to revolutionize anti-tuberculosis treatment. To be effective, current anti-tuberculosis treatments require taking several antibiotics over a minimum of 6 months and up to two years or more. ERA4TB’s goal is to replace these anti-tuberculosis treatments with ideally shorter therapies, based on modern, synergistic and safe combinations of new antibiotics. ERA4TB is one of the largest partnerships ever funded by IMI (Innovative Medicine Initiative -EU), intended to parallel all the steps to quickly identify the best combinations of antibiotics.
More than 30 universities and private partners from 13 countries are participating in this project. Among them, four research teams from the Institut Pasteur de Lille, including 3 from the CIIL, will play a decisive role in the evaluation of drug combinations, by studying their mode of action and their pharmacokinetics, key parameters to identify the best regimens. therapies for tuberculosis patients.
MCU-PH CH Tourcoing
Univ Fribourg, Suisse
Blondiaux N, Moune M, Desroses M, Frita R, Flipo M, Mathys V, Soetaert K, Kiass M, Delorme V, Djaout K, Trebosc V, Kemmer C, Wintjens R, Wohlkönig A, Antoine R, Huot L, Hot D, Coscolla M, Feldmann J, Gagneux S, Locht C, Brodin P, Gitzinger M, Déprez B, Willand N, Baulard AR.
Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420.
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Structural insights into the signalling mechanisms of two-component systems.
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Safety and immunogenicity of the live attenuated intranasal pertussis vaccine BPZE1: a phase 1b, double-blind, randomised, placebo-controlled dose-escalation study.
Lancet Infect Dis. 2020 20(11):1290-1301. Erratum in: Lancet Infect Dis. 2020 20(9):e215.
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A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region.
Nat Commun. 2020 9;11(1):2917.
Tuberculosis ; Pertussis ; Virulence ; Génomics ; Diagnostic ; Vaccines ; Drugs resistance
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