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Role in metal homeostasis of CtpD, a Co 2+ transporting P 1B4 ‐ATPase of Mycobacterium smegmatis
Author(s) -
Raimunda Daniel,
Long Jarukit E.,
Sassetti Christopher M.,
Argüello José M.
Publication year - 2012
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2012.08082.x
Subject(s) - mycobacterium smegmatis , biology , atpase , biochemistry , mutant , mycobacterium tuberculosis , intracellular , enzyme , gene , tuberculosis , medicine , pathology
Summary Genetic studies in the tuberculosis mouse model have suggested that mycobacterial metal efflux systems, such as the P 1B4 ‐ATPase CtpD, are important for pathogenesis. The specificity for substrate metals largely determines the function of these ATPases; however, various substrates have been reported for bacterial and plant P 1B4 ‐ATPases leaving their function uncertain. Here we describe the functional role of the CtpD protein of Mycobacterium smegmatis . An M. smegmatis mutant strain lacking the ctpD gene was hypersensitive to Co 2+ and Ni 2+ and accumulated these metals in the cytoplasm. ctpD transcription was induced by both Co 2+ and superoxide stress. Biochemical characterization of heterologously expressed, affinity‐purified CtpD showed that this ATPase is activated by Co 2+ , Ni 2+ and to a lesser extend Zn 2+ (20% of maximum activity). The protein was also able to bind one Co 2+ , Ni 2+ or Zn 2+ to its transmembrane transport site. These observations indicate that CtpD is important for Co 2+ and Ni 2+ homeostasis in M. smegmatis , and that M. tuberculosis CtpD orthologue could be involved in metal detoxification and resisting cellular oxidative stress by modulating the intracellular concentration of these metals.