Veronique Dartois, Ph.D.

Associate Professor of Medicine   |   View CV
Room RBL 2232

We are living in a perfect storm: resistance of bacteria against antibiotics is increasing and the drug discovery pipelines in industry are empty. There is an urgent medical need for the discovery and development of new antibacterials. To address this issue we established with our collaborators a fully enabled, academia based, drug discovery program comprising microbiology, structural biology, pharmacology and medicinal chemistry. Our focus is the identification of novel lead – target couples for lead optimization campaigns with the objective to deliver preclinical development compounds. The disease area of interest is lung disease caused by M. tuberculosis and Non-Tuberculous Mycobacteria (NTM), including M. abscessus and M. avium. Current tuberculosis projects include: next generation pyrazinamide and bedaquiline; microbiota metabolite indole propionic acid; DHFR inhibitors and membrane targeting alkyl indoles. NTM strategies include: repurposing (ribabutin, novel synergies); repositioning (oxazolidinones) and de novo drug discovery via various whole screen screens of TB active libraries, followed by parallel hit-to-lead and target deconvolution. In addition to carrying out drug discovery projects we are developing more predictive in vitro and ex vivo assays for NTM disease and a bacterial cell pharmacokinetic platform.

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Tiwari D, Park SW, Essawy MM, Dawadi S, Mason A, Nandakumar M, Zimmerman M, Mina M, Ho HP, Engelhart CA, Ioerger T, Sacchettini JC, Rhee K, Ehrt S, Aldrich CC, Dartois V, Schnappinger D (2018) Targeting protein biotinylation enhances tuberculosis chemotherapy. Sci Transl Med 10. PMI: 29695454

Sarathy JP, Via LE, Weiner D, Blanc L, Boshoff H, Eugenin EA, Barry CE, 3rd, Dartois VA (2018) Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum. Antimicrob Agents Chemother 62. PMI: 29203492

Chen C, Gardete S, Jansen RS, Shetty A, Dick T, Rhee KY, Dartois V (2018) Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis. Antimicrob Agents Chemother 62. PMI: 29463541

Blanc L, Lenaerts A, Dartois V, Prideaux B (2018) Visualization of Mycobacterial Biomarkers and Tuberculosis Drugs in Infected Tissue by MALDI-MS Imaging. Anal Chem. PMI: 29668262

Zimmerman M, Lestner J, Prideaux B, O’Brien P, Freedman I, Chen C, Dietzold J, Daudelin I, Kaya F, Blanc L, Chen PY, Park S, Salgame P, Sarathy J, Dartois V (2017) Ethambutol partitioning in tuberculous pulmonary lesions explains its clinical efficacy. Antimicrob Agents Chemother. PMI: 28696241

Mishra BB, Lovewell RR, Olive AJ, Zhang G, Wang W, Eugenin E, Smith CM, Phuah JY, Long JE, Dubuke ML, Palace SG, Goguen JD, Baker RE, Nambi S, Mishra R, Booty MG, Baer CE, Shaffer SA, Dartois V, McCormick BA, Chen X, Sassetti CM (2017) Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat Microbiol 2: 17072. PMI: 28504669

Gopal P, Tasneen R, Yee M, Lanoix JP, Sarathy J, Rasic G, Li L, Dartois V, Nuermberger E, Dick T (2017) In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1. ACS Infect Dis 3: 492-501. PMI: 28271875

Sarathy JP, Zuccotto F, Hsinpin H, Sandberg L, Via LE, Marriner GA, Masquelin T, Wyatt P, Ray P, Dartois V (2016) Prediction of Drug Penetration in Tuberculosis Lesions. ACS Infect Dis 2: 552-563. PMI: 27626295

Marakalala MJ, Raju RM, Sharma K, Zhang YJ, Eugenin EA, Prideaux B, Daudelin IB, Chen PY, Booty MG, Kim JH, Eum SY, Via LE, Behar SM, Barry CE, 3rd, Mann M, Dartois V, Rubin EJ (2016) Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat Med 22: 531-538. PMI: 27043495

Liu Y, Tan S, Huang L, Abramovitch RB, Rohde KH, Zimmerman MD, Chen C, Dartois V, VanderVen BC, Russell DG (2016) Immune activation of the host cell induces drug tolerance in Mycobacterium tuberculosis both in vitro and in vivo. J Exp Med 213: 809-825. PMI: 27114608

Lanoix JP, Tasneen R, O’Brien P, Sarathy J, Safi H, Pinn M, Alland D, Dartois V, Nuermberger E (2016) High Systemic Exposure of Pyrazinoic Acid Has Limited Antituberculosis Activity in Murine and Rabbit Models of Tuberculosis. Antimicrob Agents Chemother 60: 4197-4205. PMI: 27139472

Irwin SM, Prideaux B, Lyon ER, Zimmerman MD, Brooks EJ, Schrupp CA, Chen C, Reichlen MJ, Asay BC, Voskuil MI, Nuermberger EL, Andries K, Lyons MA, Dartois V, Lenaerts AJ (2016) Bedaquiline and Pyrazinamide Treatment Responses Are Affected by Pulmonary Lesion Heterogeneity in Mycobacterium tuberculosis Infected C3HeB/FeJ Mice. ACS Infect Dis 2: 251-267. PMI: 27227164

Gopal P, Yee M, Sarathy J, Low JL, Sarathy JP, Kaya F, Dartois V, Gengenbacher M, Dick T (2016) Pyrazinamide Resistance Is Caused by Two Distinct Mechanisms: Prevention of Coenzyme A Depletion and Loss of Virulence Factor Synthesis. ACS Infect Dis 2: 616-626. PMI: 27759369

Dutta NK, Bruiners N, Pinn ML, Zimmerman MD, Prideaux B, Dartois V, Gennaro ML, Karakousis PC (2016) Statin adjunctive therapy shortens the duration of TB treatment in mice. J Antimicrob Chemother 71: 1570-1577. PMI: 26903278

Dartois V, Saito K, Warrier T, Nathan C (2016) New Evidence for the Complexity of the Population Structure of Mycobacterium tuberculosis Increases the Diagnostic and Biologic Challenges. Am J Respir Crit Care Med 194: 1448-1451. PMI: 27976945

Via LE, Savic R, Weiner DM, Zimmerman MD, Prideaux B, Irwin SM, Lyon E, O’Brien P, Gopal P, Eum S, Lee M, Lanoix JP, Dutta NK, Shim T, Cho JS, Kim W, Karakousis PC, Lenaerts A, Nuermberger E, Barry CE, 3rd, Dartois V (2015) Host-Mediated Bioactivation of Pyrazinamide: Implications for Efficacy, Resistance, and Therapeutic Alternatives. ACS Infect Dis 1: 203-214. PMI: 26086040

Prideaux B, Via LE, Zimmerman MD, Eum S, Sarathy J, O’Brien P, Chen C, Kaya F, Weiner DM, Chen PY, Song T, Lee M, Shim TS, Cho JS, Kim W, Cho SN, Olivier KN, Barry CE, 3rd, Dartois V (2015) The association between sterilizing activity and drug distribution into tuberculosis lesions. Nat Med. PMI: 26343800

Lakshminarayana SB, Huat TB, Ho PC, Manjunatha UH, Dartois V, Dick T, Rao SP (2015) Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB agents. J Antimicrob Chemother 70: 857-867. PMI: 25587994

Dartois V (2014) The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells. Nat Rev Microbiol 12: 159-167. PMI: 24487820

Dartois V, Barry CE, 3rd (2013) A medicinal chemists’ guide to the unique difficulties of lead optimization for tuberculosis. Bioorg Med Chem Lett 23: 4741-4750. PMI: 23910985

Kjellsson MC, Via LE, Goh A, Weiner D, Low KM, Kern S, Pillai G, Barry CE, 3rd, Dartois V (2012) Pharmacokinetic evaluation of the penetration of antituberculosis agents in rabbit pulmonary lesions. Antimicrob Agents Chemother 56: 446-457. PMI: 21986820

Subbian S, Tsenova L, O’Brien P, Yang G, Koo MS, Peixoto B, Fallows D, Dartois V, Muller G, Kaplan G (2011) Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs. PLoS Pathog 7: e1002262. PMI: 21949656

Rottmann M, McNamara C, Yeung BK, Lee MC, Zou B, Russell B, Seitz P, Plouffe DM, Dharia NV, Tan J, Cohen SB, Spencer KR, Gonzalez-Paez GE, Lakshminarayana SB, Goh A, Suwanarusk R, Jegla T, Schmitt EK, Beck HP, Brun R, Nosten F, Renia L, Dartois V, Keller TH, Fidock DA, Winzeler EA, Diagana TT (2010) Spiroindolones, a potent compound class for the treatment of malaria. Science 329: 1175-1180. PMI: 20813948