The latency global regulator DosR regulon of Mycobacterium tuberculosis, which 
is stimulated by hypoxia, comprises approximately fifty genes including ctpF 
(Rv1997), which encodes a putative alkali/alkaline earth ion transporter of the 
plasma membrane. In this work, the influence of hypoxia and M. tuberculosis DosR 
on the ATPase activity of mycobacterial plasma membrane was assessed. We 
performed bioinformatic analyses which indicated that the pma1 gene product is 
the M. smegmatis ortholog of the M. tuberculosis cation transporter CtpF. In 
addition, a possible Na(+), K(+) and/or Ca(2+) pumping mediated by Pma1 was also 
predicted. Enzymatic analyses indicated that the basal ATPase activity of plasma 
membrane vesicles from M. smegmatis cells cultured under hypoxia and 
over-expressing DosR, decreased 30 and 40 % respectively in comparison to 
oxygenated cells. In contrast, the specific Na(+)/K(+) and Ca(2+) ATPase 
activities of the plasma membrane increased 2.8- and 3.5-fold, respectively, 
under hypoxia, similar to that observed for cells over-expressing the DosR 
regulator. In agreement, RT-qPCR experiments demonstrated that the transcription 
level of the pma1 gene increased under hypoxia at levels similar to that of M. 
smegmatis cells over-expressing the M. tuberculosis DosR regulator. The entire 
findings suggest that hypoxia stimulates Na(+)/K(+) and Ca(2+) ATPase activities 
in the mycobacterial plasma membrane, and this is possibly mediated by the 
dormancy regulator DosR.