Exploring the zoonotic potential of Mycobacterium bovis using variant calling approaches

Abstract

BackgroundMycobacterium tuberculosis var. bovis is one of the causative agents of Tuberculosis primarily known to infect cattle and is a member of the Mycobacterium Tuberculosis Complex. M.bovis is zoonotic and infects human and other animals resulting in immense economic losses globally. M.bovis is often misdiagnosed and becomes a challenge for treatment and recovery, as M.bovis is intrinsically resistant to certain antibiotics. Hence, the need for accurate diagnostics for zoonotic tuberculosis. ResultsIn order to discern the differences which lie between M.tuberculosis and M.bovis isolates we collected a global collection of M.bovis isolates from NCBI and carried out variant identification studies keeping M.tuberculosis as the reference. Clustering approaches like Principal component analysis and distance-based UPGMA methods helped to segregate isolates into different clusters of homogeneous and heterogeneous populations, which were further analyzed for variant identification. Methods like Joint Variant Calling using population-based studies was adopted for the M.bovis strains, which helped to discern high confidence polymorphisms for each set of populations. Four different variant callers were used to predict SNPs present in their genomic regions. Based on the predicted SNPs, M.bovis samples isolated from New-Zealand were identified as a heterogeneous fast evolving population, whereas the UK samples were identified as a slow evolving homogeneous population. The core-SNP identified for each population revealed the “fixed” mutations present within the populations, whereas, the total-SNP for heterogeneous population indicated presence of clonal subpopulations. A methodology for assignment of genomic coordinates to the reference SNP cluster id of M.tuberculosis entries in dbSNP was also developed and implemented, which helped to identify the percentage of known variants in a population. ConclusionsPopulation-specific studies for global collection of M.bovis samples aided in identification of SNPs responsible for zoonosis. The core-SNP set identified across global M.bovis isolates provide a rationale for further studies to the underlying host-tropism along with aiding in as a robust genetic biomarker for distinguishing M.bovis form M.tuberculosis in addition to the already known RDs. The variation profile reported in this study can serve as potential biomarkers for identification of M.bovis isolates and provide a rationale for further studies to the underlying host-tropism.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas

“…Likewise, whole genome sequencing (WGS) strategies for outbreak investigations, molecular epidemiology and surveillance have significantly advanced our understanding on mycobacteria transmissions [ 13 ]. These novel approaches can also provide insights on biomarkers associated with traits such as virulence and tropism [ 14 , 15 ]. Here, we performed a comprehensive analysis aimed to identify high confidence drug resistance mutation among 2,074 M .…”