P071

1:Research Center Borstel

Treatment failure remains a critical challenge in the global fight against tuberculosis (TB), leading not only to poor clinical outcomes but also to continued disease transmission. While antibiotic resistance has long been recognised as a major contributor, increasing evidence points to drug tolerance as an additional, underappreciated factor. Drug-tolerant Mycobacterium tuberculosis complex (MTBC) bacteria exhibit prolonged survival during antibiotic treatment. We hypothesise that tolerance mechanisms are greater in strains from certain lineages (or sub-lineages), which may explain variations in antibiotic resistance rates as well as epidemiological success.

In this study, we examine the tolerance of 12 strains representing MTBC lineages 2.2.1 (Beijing Central Asia) and 4.1.2.1 (Euro American Haarlem) plus H37Rv, using time-kill assays with increasing concentrations of rifampicin. Our results show that strains of Lineage 4 exhibit slower drug killing, thus greater tolerance as compared to Lineage 2 strains and H37Rv. This suggests that Lineage 4 strains employ a tolerance-based survival strategy, as opposed to the resistance-based strategy observed in Lineage 2 strains.

These findings underscore the need to integrate lineage-specific tolerance profiles into TB treatment strategies and diagnostics.