Whole Genome Sequencing Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics of Mycobacterium bovis From Chinese Farms

Introduction Bovine tuberculosis (bTB) has a certain incidence on farms in China, but little is known about its prevalence and the pathogenic Mycobacterium species. With the increasing application of whole-genome sequencing (WGS), it is now possible to investigate the genomic diversity, lineage distribution, and drug resistance profiles of M. bovis at high resolution. Methods In this study, we sequenced 29 Mycobacterium tuberculosis complex (MTBC) isolates from two farms in China and incorporated genomic data from 79 publicly available M. bovis isolates from cattle farms in China for a comprehensive genomic analysis. Results The majority of the 106 M. bovis isolates (63.2%, 67/106) belong to lineage La1.4. The dataset was screened for isolates of two known clonal complexes, Eu1 and Eu3, corresponding to La1.8.1 and La1.2, respectively. In silico spoligotyping revealed nine previously identified profiles, and the most common spoligotype in this study is SB1903. All isolates have the H57D mutation in the pncA gene associated with pyrazinamide (PZA) resistance. 16.0% (17/106) of isolates have resistance mutations to first- or second-line drugs other than PZA, with one isolate classified as pre-XDR-TB. The distribution of cluster strains suggests the possibility of recent transmission and outbreak in the two farms. It is noted that two M. tuberculosis isolates from tissue samples had detectable drug resistance mutations. Conclusion The results of this study provide the basis for in-depth analysis of genomic population characteristics and drug resistance of M. bovis in China. It should be noted that close contact between humans and cattle increases the risk of M. tuberculosis transmission from humans to cattle in rural areas or developing countries with low levels of human-animal separation.