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Rifampicin tolerance in Mycobacterium tuberculosis complex strains

A Hintz-Rüter(1) L Sonnenkalb(1) S Niemann(1)

1:Reseach Center Borstel

The evolution of drug resistance in Mycobacterium tuberculosis (Mtb) poses a substantial threat to the successful treatment of tuberculosis (TB) and the global fight against TB. Recent studies indicate that the development of antibiotic tolerance is a stepping stone for resistance acquisition of Mycobacterium tuberculosis complex (MTBC) strains. Tolerant bacteria exhibit prolonged survival under antibiotic treatment, facilitated by genetic or transcriptomic mechanisms. We hypothesize that the tolerance capability is greater in strains of some lineages (or sub-lineages), which could explain differences in antibiotic resistance rates as well as epidemiological success.

In this work, we investigate the tolerance of multiple strains representing MTBC lineages 2 (Beijing) and 4 (Haarlem) using time-kill assays under different concentrations of rifampicin (RIF). The results revealed that strains of Lineage 4 displayed a greater tolerance compared to strains of Lineage 2. However, it is noteworthy that one of the Lineage 2 strains exhibited a comparable level of tolerance to that observed in the Lineage 4 strains.

In future research, we will further analyse time-kill assay data to define resilient vs. resistant populations which arose in these experiments. This will be achieved by comparing colony-forming units, live-dead staining and flow cytometry.

This investigation underscores the importance of understanding antibiotic tolerance as a precursor to drug resistance acquisition in the complex phylogeny of MTBC strains.

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