Wollenberg K, Harris M, Gabrielian A, et al. - Via performing a retrospective analysis of Mycobacterium tuberculosis from Moldova, researchers sought to better understand the genomic basis of drug resistance and its effect on the determination of recurrence status in a high DR-burden environment. From 189 patients, 278 isolates were collected and were analyzed for genomes; 87 patients were sampled longitudinally. Using Illumina technology, pathogen genomes were sequenced; SNP panels were generated for each sample for use in phylogenetic and network analysis. Among drug-resistant tuberculosis (DR-TB) samples, they identified clusters of multiple patients with 10 or fewer differences, which is evidence of person-to-person transmission of DR-TB. Analyzing longitudinally collected isolates, little change was observed over time in many infections, though there were 35 patients demonstrating reinfection by divergent (number of differences > 10) lineages. Additionally, there were several same-lineage sample pairs with higher divergence than expected for a relapsed infection. They noted very close relationships among 61 of these samples in network analysis of the H3/4.2.1 clade, making differentiation of reactivation and reinfection difficult. Genomic profile and clinical drug sensitivity test results were discordant in twelve samples; four of these had low level (but not statistically significant) variation at DR SNPs implying low-level mixed infections. The findings suggest the more frequent occurrence of reinfection than currently recognized. Increased evidence of mixed infection was identified, which could be more robustly characterized with deeper levels of genomic sequencing.