An African origin for Mycobacterium bovis

Abstract

Background and objectives Mycobacterium bovis and Mycobacterium caprae are two of the most important agents of tuberculosis in livestock and the most important causes of zoonotic tuberculosis in humans. However, little is known about the global population structure, phylogeography and evolutionary history of these pathogens. Methodology We compiled a global collection of 3364 whole-genome sequences from M.bovis and M.caprae originating from 35 countries and inferred their phylogenetic relationships, geographic origins and age. Results Our results resolved the phylogenetic relationship among the four previously defined clonal complexes of M.bovis, and another eight newly described here. Our phylogeographic analysis showed that M.bovis likely originated in East Africa. While some groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world. Conclusions and implications Our results allow a better understanding of the global population structure of M.bovis and its evolutionary history. This knowledge can be used to define better molecular markers for epidemiological investigations of M.bovis in settings where whole-genome sequencing cannot easily be implemented. Lay summary During the last few years, analyses of large globally representative collections of whole-genome sequences (WGS) from the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages have enhanced our understanding of the global population structure, phylogeography and evolutionary history of these pathogens. In contrast, little corresponding data exists for M. bovis, the most important agent of tuberculosis in livestock. Using whole-genome sequences of globally distributed M. bovis isolates, we inferred the genetic relationships among different M. bovis genotypes distributed around the world. The most likely origin of M. bovis is East Africa according to our inferences. While some M. bovis groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world driven by cattle movements.

Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex

“…This, in turn, is a function of how deeply rooted this phenotype is in the phylogenetic tree of MTBC and how well these strains have subsequently transmitted. For example, the pncA H57D mutation, which is estimated to have evolved approximately 900 years ago [44], is shared by the vast majority of M. bovis strains and consequently renders them intrinsically resistant to PZA [45]. Yet, owing to the control policies introduced in well-resourced countries over the past century, M. bovis is responsible for fewer than 3% of human tuberculosis (TB) cases globally [46].…”

New insights into the mycobacterial PE and PPE proteins provide a framework for future research

“…The RD5 deletions in the larger livestock animals such as cattle and goats could potentially be explained by the artificially shortened lifespans due to consumption of these animals. However, it is unclear to what extend this is true for the time in which the most‐recent common ancestor of M. bovis and M. caprae emerged (Loiseau et al , ). In line with the hypothesis that RD5‐deletions make M. bovis more virulent, there is experimental evidence that M. bovis is more aggressive in cattle compared to M. tuberculosis (Whelan et al , ).…”

Population structure and transmission ofMycobacterium bovisin Ethiopia

“…Clonal complexes were assigned to samples using RDanalyzer v1.0 [36] with samples not identified as belonging to previously described M. bovis clonal complexes (European 1 (Eu1), European 2 (Eu2), African 1 (Af1), and African 2 (Af2)) designated as "Other" [20,[37][38][39]. Further assignment to clonal complex was based on the phylogenetic lineages recently identified by Loiseau et al [40].…”

“…Genomes were selected based on the following criteria: they were previously published [25,40,[47][48][49][50][51] and represented the currently understood M. bovis diversity. All previously characterized clonal complexes (Af1, Af2, Eu1, Eu2, and Eu3) and uncharacterized lineages (Unknown1 to Unknown8) from Loiseau et al [40] were included. Due to the large number of available sequences for clonal complexes Eu1 and Eu2, a random selection of 100 genomes was chosen for each.…”