Polyketide synthases mutation in tuberculosis transmission revealed by whole genomic sequence, China, 2011-2019.

Tuberculosis (TB) is an infectious disease caused by a bacterium called (). Previous studies have primarily focused on the transmissibility of multidrug-resistant (MDR) or extensively drug-resistant (XDR) . However, variations in virulence across lineages may also account for differences in transmissibility. In , polyketide synthase (PKS) genes encode large multifunctional proteins which have been shown to be major mycobacterial virulence factors. Therefore, this study aimed to identify the role of PKS mutations in TB transmission and assess its risk and characteristics. Whole genome sequences (WGSs) data from 3,204 isolates was collected from 2011 to 2019 in China. Whole genome single nucleotide polymorphism (SNP) profiles were used for phylogenetic tree analysis. Putative transmission clusters (≤10 SNPs) were identified. To identify the role of PKS mutations in TB transmission, we compared SNPs in the PKS gene region between "clustered isolates" and "non-clustered isolates" in different lineages. Cluster-associated mutations in and were identified among different lineage isolates. They were statistically significant among clustered strains, indicating that they may enhance the transmissibility of . Overall, this study provides new insights into the function of PKS and its localization in . The study found that ppsA, pks12, and pks13 may contribute to disease progression and higher transmission of certain strains. We also discussed the prospective use of mutant , , and genes as drug targets.