Mycobacterium bovis: From Genotyping to Genome Sequencing

Abstract

Mycobacterium bovis is the main pathogen of bovine, zoonotic, and wildlife tuberculosis. Despite the existence of programs for bovine tuberculosis (bTB) control in many regions, the disease remains a challenge for the veterinary and public health sectors, especially in developing countries and in high-income nations with wildlife reservoirs. Current bTB control programs are mostly based on test-and-slaughter, movement restrictions, and post-mortem inspection measures. In certain settings, contact tracing and surveillance has benefited from M. bovis genotyping techniques. More recently, whole-genome sequencing (WGS) has become the preferential technique to inform outbreak response through contact tracing and source identification for many infectious diseases. As the cost per genome decreases, the application of WGS to bTB control programs is inevitable moving forward. However, there are technical challenges in data analyses and interpretation that hinder the implementation of M. bovis WGS as a molecular epidemiology tool. Therefore, the aim of this review is to describe M. bovis genotyping techniques and discuss current standards and challenges of the use of M. bovis WGS for transmission investigation, surveillance, and global lineages distribution. We compiled a series of associated research gaps to be explored with the ultimate goal of implementing M. bovis WGS in a standardized manner in bTB control programs.

Genetic Diversity and Potential Paths of Transmission of Mycobacterium bovis in the Amazon: The Discovery of M. bovis Lineage Lb1 Circulating in South America

“…The detection of an inter-species transmission link, the intertwined phylogenetic dispersal of M. bovis obtained from cattle and buffalo, and the absence of significant difference in M. bovis genetic diversity in cattle vs . buffalo suggest that contact rate between different hosts and consequent geographic proximity likely played a more important role in determining the host range of M. bovis in this region than host species, agreeing with recent studies ( 10 , 24 ). Currently the most accepted hypothesis is that M. bovis is not a specialized pathogen, i.e., can affect several host species irrespective of its genetic makeup.…”

“…Currently, the use of whole-genome sequencing (WGS) to understand tuberculous mycobacteria populational structure is widespread and provided the basis for outbreak tracing and phylogenetic analysis resulting in the classification of human-adapted MTBC into 8 lineages, with M. tuberculosis accounting for L1 to L4 and L7-L8, and Mycobacterium africanum comprising of L5 and L6 ( 8 , 9 ). On the other hand, M. bovis has been historically classified by Clonal Complexes (CCs), which are identified by genomic deletions, few Single Nucleotide Polymorphism's (SNPs), and/or spoligotypes patterns ( 10 ). Accordingly, four different M. bovis CCs have been described presenting distinct geographical distribution patterns: African 1 and 2 restricted to Africa, European 2 commonly found in the Iberian Peninsula, and European 1 distributed globally ( 11 – 14 ).…”

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

“…The arrival of a plethora of next generation sequencing technologies has greatly facilitated the advanced characterization of mycobacterial strains in different settings as well as the identification of mutations conferring drug resistance. 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 ].…”

Single-nucleotide polymorphism-based epidemiological analysis of KoreanMycobacterium bovisisolates

“…Recently, a technique for classifying and identifying MTC strains using next-generation sequencing has been reported [ 6 7 ]. Whole-genome sequencing (WGS) was used to evaluate M. tuberculosis strains isolated from humans in an area where TB had been prevalent for several years to investigate the propagation and epidemiology of TB bacteria [ 8 9 ].…”

“…Thus, SNPs have also been used in M. bovis for typing and clustering analysis. However, SNP analysis of Korean M. bovis isolates has not been performed [ 7 15 16 17 ]. In the present study, we performed SNP analysis of Korean M. bovis isolates via WGS to facilitate typing of M. bovis strains.…”