Uncovering new vulnerabilities of the TB bacillus

Several studies have revealed key mechanisms that enable M. tuberculosis to survive within the host. IPBS researchers demonstrated that inorganic sulfate uptake is essential for bacterial survival and redox balance in the lung, identifying a new pathogen-specific therapeutic target (PNAS). In parallel, a study in the EMBO Journal uncovered effluxosomes, previously unknown membrane platforms that coordinate resistance to toxic metals, opening new avenues for antimicrobial strategies.

Other work provided structural and functional insights into virulence-associated enzymes, such as protein mannosyltransferase (Communications Biology), and revisited major drug targets like InhA, highlighting challenges and opportunities for rational drug design (ChemMedChem). At the membrane level, IPBS teams also showed how mycobacterial lipids reshape host membranes, contributing to immune modulation (Biophysical Journal).

Deciphering host-pathogen interactions and immune responses

Understanding how TB manipulates host immunity remains central. IPBS researchers showed that IL-6-producing B cells can drive monocytes toward an anti-inflammatory phenotype, potentially impairing protective immune responses (European Journal of Immunology). Another study revealed how TB-induced metabolic rewiring of macrophages promotes HIV-1 dissemination via tunneling nanotubes, identifying host metabolism as a potential therapeutic target in TB/HIV coinfection (Life Science Alliance).

These findings are complemented by broader conceptual advances, including a major review in Nature Reviews Immunology identifying key gaps in T cell-mediated immunity to TB, and a synthesis on macrophage diversity and tissue niches in TB infection (Cold Spring Harbor Perspectives in Medicine).

Innovating models and therapies

IPBS is also advancing tools and strategies to better fight TB. A review in the FEBS Journal highlights the potential of lung organoids as human-relevant models to study infection and test new treatments. On the therapeutic front, researchers identified new bioinspired lipid compounds with potent anti-TB activity (European Journal of Medicinal Chemistry), opening perspectives for next-generation antibiotics.

A strong international and translational dynamic

Beyond publications, IPBS TB research is driven by an extensive network of international collaborations and large-scale projects.

Recent highlights include:

• The launch of the LAM4RO project in Madagascar, aimed at developing non-invasive diagnostic tools for TB
• 10 years of France-Argentina collaboration on TB/HIV coinfection
• A new Indo-French program on mycobacterial biofilms, addressing bacterial persistence
• Participation in a European project on innovative immunotherapies for infectious diseases
• Two IPBS projects selected in the SAMRC/ANRS MIE joint call on TB research between South Africa and France
• Continued involvement in ANR- and ANRS MIE-funded projects, several of which target TB biology, host responses or therapeutic strategies

These initiatives reflect IPBS’s strong positioning at the interface of basic research, global health and translational innovation.

Training, attractiveness and future leaders

IPBS also contributes to training the next generation of TB researchers. Recent distinctions include:

• The selection of Kien Lam Ung in the ATIP-Avenir program, developing research on host-pathogen interactions and glycobiology with support from the CNRS and the Fondation pour la Recherche Médicale
• The visit of Prof. Raju Mukherjee, strengthening collaborations in metabolomics applied to mycobacterial diseases

In parallel, discoveries originating from TB research continue to fuel innovation and valorization, as illustrated by recent advances in glycobiology with broader biomedical applications.

From molecular mechanisms to global health initiatives, IPBS is mobilized on all fronts to better understand, diagnose and treat tuberculosis.