OR22

1:Cooperative Institute for Research in Environmental Sciences, Boulder, CO, USA; 2:Dept. of Ecology and Evolutionary Biology, University of Colorado, Boulder, CO, USA; 3:Unit of Mycobacteriology, Institute of Tropical Medicine, Antwerp, Belgium; 4:BCCM/ITM Mycobacteria collection, Institute of Tropical Medicine, Antwerp, Belgium; 5:Department of Biosciences, Nottingham Trent University, Nottingham, UK

The genus Mycobacterium is made up of over 200 bacterial species which reside in a wide variety of environments and hosts. The full spectrum of pathogenicity (ability to invade a host) is covered within this genus, from environmental species with no reported clinical significance through to obligate pathogens such as M. tuberculosis and M. leprae. However, the exact mechanisms which determine if a Mycobacterium can infect a host and cause disease are not fully understood.

We gathered a robust dataset of closed, completed genomes that represent over 180 species of Mycobacterium to determine the genomic factors which govern the pathogenicity spectrum of this genus. We predicted the presence of phage and plasmids and constructed a genus-wide pangenome, containing a gene presence/absence pattern of each species. We placed species on a four-point pathogenicity scale from completely environmental (0) to obligate human pathogen (4) based on published clinical case reporting for each species. Using supervised machine learning approaches we then determined what gene presence/absence patterns best explain the placement of each species on this scale.

We uncovered an interconnecting pattern of 26 genes which accurately explain the pathogenicity potential of each Mycobacterium species. The functions of these genes, many of which allow for survival and proliferation in the host, include 2-methylcitrate dehydratase (prpR/prpD) and superoxide dismutase (sodA), as well as others of currently unknown function.  This work indicates that there are specific genetic factors driving mycobacterial host invasion. Such genes may serve as markers of ‘pathogenicity potential’ for newly discovered genus members.