Drug Resistance and Epidemiological Success of Modern Mycobacterium tuberculosis Lineages in Western India

Background Drivers of tuberculosis (TB) transmission in India, the country estimated to carry a quarter of the world's burden, are not well studied. We conducted a genomic epidemiology study to compare epidemiological success, host factors, and drug resistance among the 4 major Mycobacterium tuberculosis (Mtb) lineages (L1-L4) circulating in Pune, India. Methods We performed whole-genome sequencing (WGS) of Mtb sputum culture-positive isolates from participants in two prospective cohort studies and predicted genotypic susceptibility using a validated random forest model. We compared lineage-specific phylogenetic and time-scaled metrics to assess epidemiological success. Results Of the 612 isolates that met sequence quality criteria, Most were L3 (44.6%). The majority (61.1%) of multidrug-resistant isolates were L2 (P Conclusions L2 shows a higher frequency of resistance, and both L2 and L4 demonstrate evidence of higher epidemiological success than L3 or L1 in Pune. Contact tracing around TB cases and heightened surveillance of TB DR in India is a public health priority.