A New Phylogenetic Framework for the Animal-Adapted Mycobacterium tuberculosis Complex

Area of Science:

• * Microbial evolution
• * Zoonotic diseases
• * Genomics and phylogenetics

Background:

• * Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC) bacteria, affecting humans and animals.
• * At least nine MTBC members, termed ecotypes, infect non-human hosts, but their ecology and evolution are poorly understood.
• * Existing knowledge gaps hinder understanding of MTBC host adaptation and transmission dynamics.

Purpose of the Study:

• * To investigate the evolutionary history and host adaptation of animal-adapted MTBC ecotypes.
• * To establish a robust phylogenetic framework for animal-associated MTBC strains.
• * To explore the drivers of host tropism in MTBC.

Main Methods:

• * Screening of 12,886 publicly available MTBC genomes.
• * Sequencing of 17 newly identified animal-adapted MTBC strains.
• * Phylogenomic and comparative analyses of a total of 529 animal-adapted MTBC genomes.

Main Results:

• * Animal-adapted MTBC strains are paraphyletic, with some more related to human-adapted strains than other animal strains.
• * Four main animal-adapted MTBC clades were identified, potentially linked to host shifts, including cattle domestication events.
• * MTBC nucleotide diversity did not correlate with host phylogenetic distance, suggesting host contact and population dynamics drive tropism.

Conclusions:

• * The ancestor of Lineage 6 and animal-adapted MTBC was likely a generalist pathogen that adapted to various hosts.
• * Host tropism in animal-adapted MTBC is influenced by host contact rates and population demographics, not solely host relatedness.
• * This study provides a new phylogenetic framework to understand MTBC ecotype evolution and mechanisms of host range expansion.