Mtb is one of about a dozen bacterial species for which some clinical isolates are now resistant to most or all antibiotics (abx) approved for treatment of the infections they cause. Heritable antimicrobial resistance (AMR) in Mtb emerges with interruption of treatment, and the long duration of TB treatment provides many opportunities for interruption. Prolonged treatment is necessary because of nonheritable resistance, also called phenotypic tolerance or persistence, defined as the transient tolerance of bacteria in an antibiotic-sensitive population to an antibiotic during exposure to an otherwise lethal concentration of that antibiotic. In contrast to “resisters”, whose AMR is genetically encoded, “persisters” are genetically sensitive bacteria whose phenotypic tolerance allows them to survive for prolonged periods during what would otherwise be rapidly curative treatment. Our laboratory aims to identify genetic and metabolic determinants that foster phenotypic tolerance in Mtb.
After completing my PhD in the laboratory of Dr. Mamadou Daffé at the Institute of Pharmacology and Structural Biology in 2009 in Toulouse, France, I joined the laboratory of Dr. Carl Nathan at Weill Cornell Medicine in New York, USA, as a postdoctoral fellow (2009-2014), an instructor (2014-2017) and an assistant professor (2017-2018). This experience spurred a continued interest in approaching TB research through multi-disciplinary approaches—spanning microbiology, biochemistry, genetics, structural biology, time-lapse and super-resolution fluorescence photomicroscopy and quantification of observed phenotypes using computational tools.