Novel Mycobacterium tuberculosis Complex Isolate from a Wild Chimpanzee

Mireia Coscolla, Astrid Lewin, Sonja Metzger, Kerstin Maetz-Rennsing, Sébastien Calvignac-Spencer, Andreas Nitsche, Pjotr Wojtek Dabrowski, Aleksandar Radonic, Stefan Niemann, Julian Parkhill, Emmanuel Couacy-Hymann, Julia Feldman, Iñaki Comas, Christophe Boesch, Sebastien Gagneux¹, and Fabian H. Leendertz¹

Author affiliations: Swiss Tropical and Public Health Institute, Basel, Switzerland (M. Coscolla, J. Feldman, S. Gagneux); University of Basel, Basel (M. Coscolla, J. Feldman, S. Gagneux); Centro Superior de Investigación en Salud Pública, Valencia, Spain (M. Coscolla, I. Comas); Robert Koch-Institut, Berlin, Germany (A. Lewin, S. Metzger, S. Calvignac-Spencer, A. Nitsche, P. Wojtek Dabrowski, A. Radonic, F.H. Leendertz); Max-Planck-Institute for Evolutionary Anthropology, Leipzig, Germany (S. Metzger, C. Boesch); German Primate Center, Goettingen, Germany (K. Maetz-Rennsing); Research Centre Borstel, Borstel, Germany (S. Niemann); Wellcome Trust Sanger Institute, Cambridge, UK (J. Parkhill); Laboratoire Nationale de la Pathologie Animale, Bingerville, Côte d’Ivoire (E. Couacy-Hymann); CIBER in Epidemiology and Public Health, Barcelona, Spain (I. Comas)

Abstract

Tuberculosis (TB) is caused by gram-positive bacteria known as the Mycobacterium tuberculosis complex (MTBC). MTBC include several human-associated lineages and several variants adapted to domestic and, more rarely, wild animal species. We report an M. tuberculosis strain isolated from a wild chimpanzee in Côte d’Ivoire that was shown by comparative genomic and phylogenomic analyses to belong to a new lineage of MTBC, closer to the human-associated lineage 6 (also known as M. africanum West Africa 2) than to the other classical animal-associated MTBC strains. These results show that the general view of the genetic diversity of MTBC is limited and support the possibility that other MTBC variants exist, particularly in wild mammals in Africa. Exploring this diversity is crucial to the understanding of the biology and evolutionary history of this widespread infectious disease.

Tuberculosis (TB) is caused by closely related acid-fast bacteria known as the Mycobacterium tuberculosis complex (MTBC) (1). MTBC includes the typical human-associated pathogens M. tuberculosis and M. africanum (2); M. canettii and other so-called “smooth TB bacilli” (3), the actual host range of which remains unknown; and several lineages adapted to different mammal species that include M. bovis, M. microti, M. caprae, M. orygis, and M. pinnipedii (4–6). Because of the wider host range of animal-associated MTBC, the common view until a decade ago was that human TB strains had evolved from M. bovis, the typical agent of bovine TB. Recent comparative genomic analyses have challenged this view by showing that animal MTBC strains nest within the genetically more diverse human MTBC strains (4,7–9). These results not only contradict the hypothesis of an animal origin for human MTBC but also promote an alternative scenario for a human origin of animal MTBC (10). However, little is known about MTBC diversity in domestic animals, and even less about MTBC diversity in wildlife, including our phylogenetically closest relatives, the great apes. Of note, novel members of MTBC affecting wild mammals in Africa have recently been discovered (11,12), a finding that suggests animal MTBC is more diverse than previously thought.
We report microbiologically confirmed MTBC infection in a wild chimpanzee. We show that this infection was caused by a divergent MTBC strain that does belong to the clade that includes M. bovis and all other animal-associated members of MTBC but is more closely related to human-associated lineage 6 (also known as M. africanum West Africa type 2 [WA2]). This finding highlights critical gaps in knowledge of MTBC diversity and indicates that African wildlife, and more particularly nonhuman primates, are potential hosts of novel MTBC variants.