Insights into ancestry and adaptive evolution of theMycobacterium tuberculosiscomplex from analysis of the emerging pathogenMycobacterium riyadhense
Authors: Guan Qingtian , Garbati Musa , Mfarrej Sara , AlMutairi Talal , Smyth Alicia , Singh Albel , Fagbo Shamsudeen , Browne John A. , Amin urRahman Muhammad , Alruwaili Alya , Hoosen Anwar , Meehan Conor J , Nakajima Chie , Suzuki Yasuhiko , Bhatt Apoorva , Gordon Stephen V. , AlAsmari Faisal , Pain A. 
Published: August 2019

AbstractCurrent evolutionary scenarios posit the emergence ofMycobacterium tuberculosis, the deadliest bacterial pathogen for humans globally, from an environmental saprophyte through a cumulative process of genome adaptation.Mycobacterium riyadhenseis a novel non-tuberculous mycobacterium (NTM) that is being increasingly isolated from human clinical cases with tuberculosis (TB)-like symptoms in various parts of the world. We provide evidence here thatM. riyadhenseis likely a ‘missing link’ in our understanding of the evolution ofM. tuberculosis. To elucidate the genomic hallmarks that define the evolutionary relationship betweenM. riyadhenseand other mycobacterial species, including members of theMycobacterium tuberculosiscomplex (MTBC), eight clinical isolates ofM. riyadhensewere sequenced and analyzed. We show, among other features, thatM. riyadhenseshares a large number of conserved orthologues with the MTBC; contains linear and circular plasmids carrying type IV and type VII secretion systems; and shows expansion of toxin/anti-toxin pairs. We conclude thatM. riyadhenseis an emerging mycobacterial pathogen that shares a common ancestor with members of the MTBC and that can serve as an experimental model to study the evolution and pathogenesis of tubercle bacilli.Author summaryMycobacterium tuberculosisis one of the most prolific infectious killers in humans and is a member of theMycobacterium tuberculosiscomplex (MTBC) - a group of genetically related pathogens that cause tuberculosis (TB) in mammalian species. It is postulated that MTBC has evolved from a free-living environmental ancestor into an obligate pathogen. In this evolutionary context, a comprehensive understanding of the genomic hallmarks of the free-living environmental ancestors of the MTBC is of particular scientific interest for better understanding of the evolution of the MTBC.Mycobacterium riyadhenseis a novel environmental mycobacterium, first isolated in 2009 in a hospital in Riyadh, that is increasingly being isolated from clinical cases with typical tuberculosis (TB)-like symptoms in humans. In this study, we report the characterization of eight clinical isolates ofM. riyadhense, compare their genomes to members of the MTBC, and provide a comprehensive insight into the adaptive changes associated with the evolution of the MTBC from environmental mycobacteria. We show thatM. riyadhenseis one of the closest known environmental mycobacteria related to the MTBC, and we provide several lines of molecular evidence thatM. riyadhenseis likely the ‘missing link’ in the evolution ofM. tuberculosis. It shares a common ancestor with members of the MTBC that have evolved through a process of genome reduction, expansion of toxin/antitoxin (T/A) gene systems, and ultimately host adaptation.