Comparative growth kinetics and drug susceptibility of Mycobacterium tuberculosis lineages prevalent in Ethiopia: implications for tuberculosis treatment and management

Tuberculosis (TB) remains a global health challenge, with treatment outcomes influenced by the genetic diversity of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strains. This study examines the growth kinetics and drug susceptibility of <i>Mtb</i> strains from different lineages in Ethiopia to understand their impact on disease management. <i>Mtb</i> strains, including sub-lineages 4.1.2.1, 4.2.2.2, 4.6.3, lineages 3 and 7, and the reference strain H37Rv (ATCC 27294), were cultured in liquid 7H9 Middlebrook broth. Growth began on day 6 post-inoculation. Sub-lineage 4.1.2.1 showed rapid exponential growth by day 9, reaching the stationary phase by day 15. Sub-lineage 4.1.2.1 followed by sub-lineage 4.2.2.2 had the highest maximum growth concentration (<i>C</i> _max), indicating enhanced growth efficiency and adaptive traits that may increase their pathogenicity or resistance to host defenses or anti-TB drugs. To support this observation, the minimum inhibitory concentrations (MIC) for first-line anti-TB drugs were assessed for all the studied <i>Mtb</i> strains using the microdilution broth method. While all strains were susceptible, MIC values varied. Sub-lineages 4.1.2.1 and 4.2.2.2 had MIC values matching WHO's critical concentrations (except for rifampicin). Lineage 3 showed increased sensitivity to rifampicin, isoniazid, and streptomycin, requiring only half the standard concentration. Lineage 7 also exhibited higher sensitivity to rifampicin and streptomycin. These findings highlight the importance of considering lineage-specific differences in <i>Mtb</i> strains for optimizing treatment regimens and improving TB control strategies, particularly in regions with diverse <i>Mtb</i> populations like Ethiopia.