Abstract
BackgroundP-type ATPases hydrolyze ATP and release energy that is used in the transport of ions against electrochemical gradients across plasma membranes, making these proteins essential for cell viability. Currently, the distribution and function of these ion transporters in mycobacteria are poorly understood.ResultsIn 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.ConclusionsThe 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.
Highlights
P-type ATPases hydrolyze ATP and release energy that is used in the transport of ions against electrochemical gradients across plasma membranes, making these proteins essential for cell viability
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, M. africanum, M. microti, M. canettii, and M. pinnipedii, which produces TB in humans and some animal hosts [2,3]
An unusually high number of cation transporter P-type ATPases are present in the Mycobacterium tuberculosis complex Multiple alignments of 128 reported P-type ATPase protein sequences from a representative group of eukaryotic and prokaryotic cells allowed the identification of highly conserved regions within the family and the classification of these members according to ion transport
Summary
P-type ATPases hydrolyze ATP and release energy that is used in the transport of ions against electrochemical gradients across plasma membranes, making these proteins essential for cell viability. Part of the infected population will develop active TB, The emergence of multidrug and extensively drugresistant tuberculosis strains (MDR-TB and XDR-TB) and the lack of drugs against latent TB have become serious problems for TB control. The identification of new therapeutic targets useful in the development of novel drugs and vaccines against latent TB is essential. New anti-TB drugs, such as diarylquinolines (TMC207) and benzothiazines (BTZ043) target essential membrane proteins that affect mycobacterial viability [6]. Antimicrobials designed against proteins of plasma membrane are ideal because they avoid problems related to membrane permeability
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