In silico identification and characterization of the ion transport specificity for P-type ATPases in the Mycobacterium tuberculosis complex

In this study, probabilistic profiles were constructed based on hidden Markov models to identify and classify P-type ATPases in the Mycobacterium tuberculosis complex (MTBC) according to the type of ion transported across the plasma membrane. Topology, hydrophobicity profiles and conserved motifs were analyzed to correlate amino acid sequences of P-type ATPases and ion transport specificity. Twelve candidate P-type ATPases annotated in the M. tuberculosis H37Rv proteome were identified in all members of the MTBC, and probabilistic profiles classified them into one of the following three groups: heavy metal cation transporters, alkaline and alkaline earth metal cation transporters, and the beta subunit of a prokaryotic potassium pump. Interestingly, counterparts of the non-catalytic beta subunits of Hydrogen/Potassium and Sodium/Potassium P-type ATPases were not found.The high content of heavy metal transporters found in the MTBC suggests that they could play an important role in the ability of M. tuberculosis to survive inside macrophages, where tubercle bacilli face high levels of toxic metals. Finally, the results obtained in this work provide a starting point for experimental studies that may elucidate the ion specificity of the MTBC P-type ATPases and their role in mycobacterial infections.Tuberculosis (TB) is one of the most important challenges in public health maintenance throughout the world. According to the World Health Organization (WHO), 8.5-9.2 million new TB cases were estimated to have occurred in 2010 [1], and 1.2–1.5 million deaths were caused by species of the Mycobacterium tuberculosis complex (MTBC) that includes M. tuberculosis, M. bovis, M. bovis BCG (vaccine strain), M. africanum, M. microti, M. canettii, and M. pinnipedii, which produces TB in humans and some animal hosts [2,3]. Part of the infected population will develop active TB, whereas the majority of cases (approximately 90%) progress to a non-infectious disease or latent TB, where myc