DprE1, a new taxonomic marker in Mycobacteria

Among the species of the Mycobacterium genus, more than 50 have been recognized as potential human pathogens. Consequently, it is important to understand the relationships between mycobacterial species. In this context the possibility to use Mycobacterium tuberculosis dprE1 as new phylogenetic/taxonomic marker has been explored. The dprE1 gene codes for the target of some new antitubercular agents such as the Benzothiazinones (BTZ). Mutations in Cys387 residue of M. tuberculosis DprE1 are responsible for BTZ resistance. The DprE1 tree revealed that different strains of the same species shared a high degree of sequence similarity and were clustered together; it also showed the discrimination between two different clusters including species sensible or resistant to BTZ. To understand the role of DprE1, a phylogenetic analysis based on a concatamer obtained from the amino acid sequences of nine mycobacterial housekeeping genes was performed. The concatamer showed that strains belonging to the same species were clustered together, but there was no a separation between the BTZ sensitive/resistant species; consequently, this parameter is not linked to the phylogeny. In conclusion, DprE1 might represent a good taxonomic marker for the assignment of a mycobacterial isolate to a given species and it also gives insights into sensitivity/resistance to BTZ and to other drugs hitting DprE1 enzyme. Moreover, the concatamer represents a good reference phylogeny for the Mycobacterium genus.