Abstract
Tuberculosis (TB) affects humans and other animals and is caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Previous studies have shown that there are at least nine members of the MTBC infecting animals other than humans; these have also been referred to as ecotypes. However, the ecology and the evolution of these animal-adapted MTBC ecotypes are poorly understood. Here we screened 12,886 publicly available MTBC genomes and newly sequenced 17 animal-adapted MTBC strains, gathering a total of 529 genomes of animal-adapted MTBC strains. Phylogenomic and comparative analyses confirm that the animal-adapted MTBC members are paraphyletic with some members more closely related to the human-adapted Mycobacterium africanum Lineage 6 than to other animal-adapted strains. Furthermore, we identified four main animal-adapted MTBC clades that might correspond to four main host shifts; two of these clades are hypothesized to reflect independent cattle domestication events. Contrary to what would be expected from an obligate pathogen, MTBC nucleotide diversity was not positively correlated with host phylogenetic distances, suggesting that host tropism in the animal-adapted MTBC seems to be driven by contact rates and demographic aspects of the host population rather by than host relatedness. By combining phylogenomics with ecological data, we propose an evolutionary scenario in which the ancestor of Lineage 6 and all animal-adapted MTBC ecotypes was a generalist pathogen that subsequently adapted to different host species. This study provides a new phylogenetic framework to better understand the evolution of the different ecotypes of the MTBC and guide future work aimed at elucidating the molecular mechanisms underlying host range.
Highlights
Tuberculosis (TB) remains a major concern both from a global health and economic point of view
We have newly sequenced four M. orygis genomes isolated in Australia in patients of South-Asia origin (Lavender et al, 2013), two dassie bacillus genomes isolated from two Hyrax imported from South-Africa to Canada (Cousins et al, 1994; Mostowy et al, 2004), eight M. microti isolated from wild-boar in Italy (Boniotti et al, 2014), two M. bovis strains isolated from patients in Switzerland and one M. caprae of unknown origin (Supplementary Table S1)
We used a total of 56,195 variable single nucleotide positions extracted from these genome sequences to construct a phylogenetic tree rooted with M. canettii, the phylogenetically closest relative of the Mycobacterium tuberculosis complex (MTBC) (Supply et al, 2013) (Figure 1)
Summary
Tuberculosis (TB) remains a major concern both from a global health and economic point of view. Among the animal-adapted members of the MTBC, some primarily infect wild mammal species (Malone and Gordon, 2017). These include Mycobacterium microti (a pathogen of voles) (Brodin et al, 2002), Mycobacterium pinnipedii (seals and sea lions) (Cousins et al, 2003), Mycobacterium orygis (antelopes) (van Ingen et al, 2012) and the “dassie bacillus” (rock hyrax) (Mostowy et al, 2004), which have been known for a long time, as well as the more recently discovered Mycobacterium mungi (mongooses) (Alexander et al, 2010), Mycobacterium suricattae (meerkats) (Parsons et al, 2013) and the “chimpanzee bacillus” (chimpanzees) (Coscolla et al, 2013). M. tuberculosis sensu stricto is well adapted to transmit from human to human (Brites and Gagneux, 2015) and is occasionally isolated from cattle or other animals which come in contact with humans (Ameni et al, 2011; Ghodbane and Drancourt, 2013). In contrast to M. tuberculosis, M. bovis has the ability to infect and maintain infectious cycles in other reservoir species such as badgers, red deers and possums (Delahay et al, 2001; Corner et al, 2012; Palmer et al, 2012)
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