Jansy Sarathy, Ph.D., is a Research Assistant Member at the Center for Discovery and Innovation.
Dr. Sarathy’s research focuses on applying site-of-disease pharmacokinetic-pharmacodynamic (PK-PD) concepts to provide a pharmacological rationale for tuberculosis treatment efficacy. Her combined research experience in both academic institutions and the pharmaceutical sector provides her with a unique perspective to drug discovery and development. Over the past decade, Dr. Sarathy has developed and optimized a series of in vitro assays that predict drug distribution in lung granulomas and drug efficacy against persistent subpopulations of Mycobacterium tuberculosis. Dr. Sarathy’s overall research goal is to facilitate the rational design of novel drugs and drug regimens for the effective treatment tuberculosis infections.
Mycobacterium tuberculosis (MTB) is a highly successful pathogen because it is well adapted to surviving in diverse host microniches with distinct environmental conditions. In particular, its ability to go into a nonreplicating drug persistent (NRP) state in response to stresses encountered in the host is a major impediment to curing the disease. The necrotic core of tuberculous lesions and cavities, commonly referred to as caseum, are reservoirs of extracellular bacteria that are recalcitrant to antibiotic treatment. Using a combination of bacteriology, mammalian cell culture, molecular and liquid chromatography -mass spectrometry (LC-MS) techniques, Dr. Sarathy studies the metabolic state and drug susceptibility of persistent M. tuberculosis that resides in caseum. Effective eradication of this subpopulation using multidrug regimens promises to shorten the duration of tuberculosis chemotherapy and prevent disease relapse.
Caseum: a Niche for Mycobacterium tuberculosis Drug-Tolerant Persisters. Sarathy JP, Dartois V. Clin Microbiol Rev. 2020 Apr 1;33(3):e00159-19.
Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum. Sarathy JP, Via LE, Weiner D, Blanc L, Boshoff H, Eugenin EA, Barry CE 3rd, Dartois VA. Antimicrob Agents Chemother. 2018 Jan 25; 62(2).
Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis. Ernest JP, Sarathy J, Wang N, Kaya F, Zimmerman MD, Strydom N, Wang H, Xie M, Gengenbacher M, Via LE, Barry CE 3rd, Carter CL, Savic RM, Dartois V. Antimicrob Agents Chemother. 2021 Sep 17; 65(10).
Fluoroquinolone Efficacy against Tuberculosis Is Driven by Penetration into Lesions and Activity against Resident Bacterial Populations. Sarathy J, Blanc L, Alvarez N, O’Brien P, Dias-Freedman I, Mina M, Zimmerman M, Kaya F, Liang HP, Prideaux B, Dietzold J, Salgame P, Savic R, Linderman J, Kirschner D, Pienaar E, Dartois V. 2018. Antimicrob Agents Chemother. 2019 Feb; 63(5).
Prediction of Drug Penetration in Tuberculosis Lesions. Sarathy JP, Zuccotto F, Hsinpin H, Sandberg L, Via LE, Marriner GA, Masquelin T, Wyatt P, Ray P, Dartois V. ACS Infect Dis. 2016 Aug 12;2(8):552-63.