Comparative genomics and epidemic success of Mycobacterium tuberculosis lineage 4 in eastern China

BACKGROUND: Mycobacterium tuberculosis (Mtb) lineage 4 (L4) remains as a crucial component of the pathogen. Genetic factors potentiate the spread of Mtb, while the genomic feature and epidemic success at individual level of L4 strains have not been fully illustrated, especially in China. Therefore, the current study aimed to obtain additional understanding on the pan-genome architecture and transmission of the pathogen. RESULTS: The results first revealed a low proportion of soft-core genes (28.66%) and high genetic diversity for Mtb L4 strains in eastern China. The pan-genome size increased with added genomes following an exponential growth trend, with no obvious plateau observed. Additionally, our results suggested a greater gene loss rate (mean: 0.0112) compared to gene gain rate (mean: 0.0039), suggesting its important roles in the course of adaptive evolution for L4 strains. Pan-genome was enriched in 120 KEGG pathways, of which the majority was metabolism (75.57%). Furthermore, we identified significant associations between the bacterial success and 5 genes (espK, ilvD, mazF7, aftD, ilvA), the presence of which suggested high transmissibility of L4 strains. CONCLUSION: This study highlights an open and dynamic pan-genome structure of Mtb L4 strains in eastern China. The local strains are undergoing massive changes in gene families that shape its gene repertoires, thereby potentially conferring the adaptive potential to environment and bacterial transmission. Collectively, our findings allow for deeper insights into the pan-genome composition, phylogenetic relationship, evolutionary dynamic, and epidemic success of Mtb L4 strains.