Systems Biology of Bacterial Antibiotic Resistance Mechanisms
Emerging Team
Our laboratory studies the molecular mechanisms of antibiotic tolerance — the ability of bacterial populations to survive, but not grow, for prolonged periods upon exposure to lethal antibiotic concentrations, in the absence of resistance. Working in Mycobacterium tuberculosis and Gram-negative bacteria, notably Klebsiella pneumoniae, we ask not only whether a drug stops bacterial growth, but how fast it kills. Because tolerance can arise through a large number of distinct physiological routes, we focus on identifying molecular convergence points — nexuses where multiple slow-killing mechanisms coalesce — that can be prioritised for drug development. Ultimately, we aim to define mechanism-convergent, drug-agnostic determinants of tolerance across bacterial species, for improved treatment outcomes and for genomic diagnostics able to anticipate resistance development.
Lab members
Publications
Mtb-Timer: a fluorescent reporter to visualize *Mycobacterium tuberculosis* replication and antibiotic responses. Víctor Campo-Pérez, Chak Hon Luk, et al., mSystems 2026. DOI: 10.1128/msystems.01796-25
Fast-growing intracellular Mycobacterium tuberculosis populations evade antibiotic treatment. Nathan Day, Baptiste Pradel, ..., Julien Vaubourgeix, et al., Nature Communications 2026. DOI: 10.1038/s41467-026-75915-8
Alanine dependence of trans-translation contributes to riboregulation of mycobacterial antibiotic recalcitrance genes. Andrea Majstorović, Hélène Botella, ..., Julien Vaubourgeix, bioRxiv 2025. DOI: 10.1101/2025.10.10.681568
Reframing antimicrobial resistance as a continuous spectrum of manifestations. Sarah Schrader, Hélène Botella, Julien Vaubourgeix, Current Opinion in Microbiology 2023. DOI: 10.1016/j.mib.2022.102259
Multiform antimicrobial resistance from a metabolic mutation. Sarah Schrader, Hélène Botella, ..., Julien Vaubourgeix, Science Advances 2021. DOI: 10.1126/sciadv.abh2037
Biology of antimicrobial resistance and approaches to combat it. Sarah Schrader, Julien Vaubourgeix, et al., Science Translational Medicine 2020. DOI: 10.1126/scitranslmed.aaz6992
Nonredundant functions of Mycobacterium tuberculosis chaperones promote survival under stress. Alexa P. Harnagel, Landys Lopez Quezada, ..., Julien Vaubourgeix, et al., Molecular Microbiology 2020. DOI: 10.1111/mmi.14615
Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition. Elaine Ballinger, John Mosior, ..., Julien Vaubourgeix, et al., Science 2019. DOI: 10.1126/science.aau8959
Intestinal Bile Acids Induce a Morphotype Switch in Vancomycin-Resistant Enterococcus that Facilitates Intestinal Colonization. Peter T. McKenney, Jinyuan Yan, Julien Vaubourgeix, et al., Cell Host & Microbe 2019. DOI: 10.1016/j.chom.2019.03.008
Persistent Mycobacterium tuberculosis infection in mice requires PerM for successful cell division. Ruojun Wang, Kaj M. Kreutzfeldt, ..., Julien Vaubourgeix, et al., eLife 2019. DOI: 10.7554/elife.49570
Targeting the Proteostasis Network for Mycobacterial Drug Discovery. Tania J. Lupoli, Julien Vaubourgeix, et al., ACS Infectious Diseases 2018. DOI: 10.1021/acsinfecdis.7b00231
Building Walls: Work That Never Ends. Hélène Botella, Julien Vaubourgeix, Trends in Microbiology 2018. DOI: 10.1016/j.tim.2018.11.006
Mycobacterium tuberculosis protease MarP activates a peptidoglycan hydrolase during acid stress. Hélène Botella, Julien Vaubourgeix, et al., The EMBO Journal 2017. DOI: 10.15252/embj.201695028
Distinct Spatiotemporal Dynamics of Peptidoglycan Synthesis between Mycobacterium smegmatis and Mycobacterium tuberculosis. Hélène Botella, Guangli Yang, ..., Julien Vaubourgeix, mBio 2017. DOI: 10.1128/mbio.01183-17
Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death. Laure Botella, Julien Vaubourgeix, et al., Nature Communications 2017. DOI: 10.1038/ncomms14731
Stressed Mycobacteria Use the Chaperone ClpB to Sequester Irreversibly Oxidized Proteins Asymmetrically Within and Between Cells. Julien Vaubourgeix, Gang Lin, et al., Cell Host & Microbe 2015. DOI: 10.1016/j.chom.2014.12.008
Disruption of an M. tuberculosis Membrane Protein Causes a Magnesium-dependent Cell Division Defect and Failure to Persist in Mice. Nichole Goodsmith, Xinzheng V. Guo, ..., Julien Vaubourgeix, et al., PLOS Pathogens 2015. DOI: 10.1371/journal.ppat.1004645
N,C-Capped Dipeptides with Selectivity for Mycobacterial Proteasome over Human Proteasomes: Role of S3 and S1 Binding Pockets. Gang Lin, Tamutenda Chidawanyika, ..., Julien Vaubourgeix, et al., Journal of the American Chemical Society 2013. DOI: 10.1021/ja400021x
A Common Mechanism of Inhibition of the Mycobacterium tuberculosis Mycolic Acid Biosynthetic Pathway by Isoxyl and Thiacetazone. Anna E. Grzegorzewicz, Jana Korduláková, ..., Julien Vaubourgeix, et al., Journal of Biological Chemistry 2012. DOI: 10.1074/jbc.m112.400994
Deciphering sulfoglycolipids of Mycobacterium tuberculosis. Emilie Layre, D. Cala-De Paepe, ..., Julien Vaubourgeix, et al., Journal of Lipid Research 2011. DOI: 10.1194/jlr.m013482
Functional characterization of the Mycobacterium tuberculosis serine/threonine kinase PknJ. Jichan Jang, Alexandre Stella, ..., Julien Vaubourgeix, et al., Microbiology 2010. DOI: 10.1099/mic.0.038133-0
S-Adenosyl-N-decyl-aminoethyl, a Potent Bisubstrate Inhibitor of Mycobacterium tuberculosis Mycolic Acid Methyltransferases. Julien Vaubourgeix, F. Bardou, et al., Journal of Biological Chemistry 2009. DOI: 10.1074/jbc.m809599200
Foamy Macrophages from Tuberculous Patients' Granulomas Constitute a Nutrient-Rich Reservoir for M. tuberculosis Persistence. Pascale Peyron, Julien Vaubourgeix, et al., PLoS Pathogens 2008. DOI: 10.1371/journal.ppat.1000204
