Patterns and Processes of Mycobacterium bovis Evolution Revealed by Phylogenomic Analyses

Abstract

Mycobacterium bovis is an important animal pathogen worldwide that parasitizes wild and domesticated vertebrate livestock as well as humans. A comparison of the five M. bovis complete genomes from the United Kingdom, South Korea, Brazil, and the United States revealed four novel large-scale structural variations of at least 2,000 bp. A comparative phylogenomic study including 2,483 core genes of 38 taxa from eight countries showed conflicting phylogenetic signal among sites. By minimizing this effect, we obtained a tree that better agrees with sampling locality. Results supported a relatively basal position of African strains (all isolated from Homo sapiens), confirming that Africa was an important region for early diversification and that humans were one of the earliest hosts. Selection analyses revealed that functional categories such as “Lipid transport and metabolism,” “Cell cycle control, cell division, chromosome partitioning” and “Cell motility” were significant for the evolution of the group, besides other categories previously described, showing importance of genes associated with virulence and cholesterol metabolism in the evolution of M. bovis. PE/PPE genes, many of which are known to be associated with virulence, were major targets for large-scale polymorphisms, homologous recombination, and positive selection, evincing for the first time a plethora of evolutionary forces possibly contributing to differential adaptability in M. bovis. By assuming different priors, US strains originated and started to diversify around 150–5,210 ya. By further analyzing the largest set of US genomes to date (76 in total), obtained from 14 host species, we detected that hosts were not clustered in clades (except for a few cases), with some faster-evolving strains being detected, suggesting fast and ongoing reinfections across host species, and therefore, the possibility of new bovine tuberculosis outbreaks.

Detection of a streptomycin-resistant Mycobacterium bovis strain through antitubercular drug susceptibility testing of Tunisian Mycobacterium tuberculosis complex isolates from cattle

“…M. bovis has one of the broadest host ranges of any known zoonotic pathogen and is globally distributed [ 9 ]. The phylogenomic analysis of M. bovis genomes has recently revealed large-scale polymorphisms, which may contribute to the differential adaptability of the pathogen [ 10 ]. M. bovis is naturally resistant to pyrazinamide (PZA) [ 11 ], which is one of the first-line antibiotics used to treat tuberculosis in humans.…”

Complete Genome Sequencing of Mycobacterium bovis SP38 and Comparative Genomics of Mycobacterium bovis and M. tuberculosis Strains

“…The first performed sequencing of three M. bovis and one M. caprae genomes to correlate genomic characteristics with virulence phenotypes (e.g., lesion scores and hosts) (de la Fuente et al, 2015 ). The second evaluated the phylogenetic relatedness of 38 M. bovis genomes, identifying recombination sites, and suggesting that some North-American lineages of M. bovis evolved faster than others, which might be related to bacterial maintenance in different hosts causing new outbreaks in the USA (Patané et al, 2017 ). Thus, a more comprehensive comparative genomic study of M. bovis strains using complete and draft genomes is still lacking and should provide important data to understand the biology of this pathogen, especially when compared to M. tuberculosis .…”

Global distribution and evolution ofMycobacterium bovislineages

“…However, no studies to date have comprehensively analyzed M. bovis genomes at a global scale. Few studies that have compared transboundary M. bovis strains analyzed bacterial isolates obtained from a reduced number of countries (n<9) and included small sample sizes (Dippenaar et al, 2017; Patané et al, 2017; Zimpel et al, 2017a; Ghebremariam et al, 2018; Lasserre et al, 2018). Nevertheless, attained results suggest that M. bovis strains are likely to cluster based on geographical location (Dippenaar et al, 2017; Kraemer Zimpel et al, 2017; Lasserre et al, 2018).…”