Impact of sublineage diversity on intrinsic susceptibility of Beijing genotype Mycobacterium tuberculosis

Tuberculosis (TB) remains a significant global health issue, with drug-resistant TB posing a major challenge. The genetic lineage of Mycobacterium tuberculosis (Mtb) is known to influence various aspects, including drug resistance. Still, the relationship between different lineages and drug resistance levels, especially in the context of the Beijing genotype, requires further exploration. This study aimed to investigate the disparities in drug resistance among diverse lineages of Mtb. We analyzed 193 clinical isolates from drug-resistant TB patients, among them 91.2% were MDR/pre-XDR-TB. Samples were collected from patients at specific hospitals between 2014 and 2020. The isolates were subjected to smear microscopy, sputum culture, minimum inhibitory concentration (MIC) testing, and whole-genome sequencing (WGS). The MIC distributions and resistance levels of drugs like INH, AMK, RIF, EMB, and FQ were analyzed, and the association between lineages and drug resistance was determined using statistical tests. Our results showed significant differences in the MIC distributions and resistance levels of INH and AMK between lineages 2.2 and 2.3. Lineage 2.3.2 was a protective factor for high-level INH resistance, and lineage 2.3 was a protective factor for high-level AMK resistance. The L2.3.6 strain had a high proportion of high-level resistance to INH and AMK. This study provides evidence for the evolution and spread of the modern Beijing genotype of Mtb. It suggests that L2.3.6 will have the potential to become the main sublineage of tuberculosis for the spread of drug-resistant tuberculosis and the necessity of pedigree testing of drug-resistant strains in clinical treatment.