Whole-Genome Sequencing of Mycobacterium tuberculosis in Lebanon: Updated Genomic Insights

Objectives Lebanon is a low-burden tuberculosis (TB) country with a complex demographic context shaped by migration, socioeconomic instability, and recent healthcare disruptions. We aimed to characterize the population structure, drug resistance, and transmission dynamics of Mycobacterium tuberculosis using whole-genome sequencing (WGS).Methods WGS was performed on 218 M. tuberculosis isolates collected in Lebanon between 2018 and 2024, of which 196 passed quality control. TB-Profiler identified lineages and resistance-associated mutations, with results compared against available phenotypic drug susceptibility testing (DST) and line-probe assays (LPA). TB-Annotator provided high-resolution sub-lineage classification, phylogenomic contextualization within a global MTB dataset, and identification of genomic clusters.Results Lineage 4 predominated (71.4%), followed by Lineage 3 (15.3%), Lineage 2 (6.6%), and Lineage 1 (6.1%), with a single rare Lineage 7 isolate. Resistance-associated mutations were identified in 41.3% of isolates, including MDR-TB (7.1%) and pre-XDR-TB (2.6%). WGS-based resistance prediction showed high concordance (91.8%-100%) with phenotypic DST and LPA. Fourteen genomic clusters included 29/195 isolates (14.9%); incorporation of publicly available Lebanese genomes identified additional Lineage 4-associated clusters, supporting ongoing local transmission.Conclusion This nationwide WGS study revealed a highly diverse MTB population in Lebanon and supports the integration of WGS into routine TB surveillance and control activities.