The P-type ATPase CtpG preferentially transports Cd²⁺ across the Mycobacterium tuberculosis plasma membrane

P_1B-type ATPases are involved in heavy metal transport across the plasma membrane. Some Mycobacterium tuberculosis P-type ATPases are induced during infection, suggesting that this type of transporter could play a critical role in mycobacterial survival. To date, the ion specificity of M. tuberculosis heavy metal-transporting P_1B-ATPases is not well understood. In this work, we observed that, although divalent heavy metal cations such as Cu²⁺, Co²⁺, Ni²⁺, Zn²⁺ Cd²⁺ and Pb²⁺ stimulate the ATPase activity of the putative P_1B-type ATPase CtpG in the plasma membrane, whole cells of M. smegmatis expressing CtpG only tolerate high levels of Cd²⁺ and Cu²⁺. As indicator of the catalytic constant, Michaelis-Menten kinetics showed that CtpG embedded in the mycobacterial cell membrane has a V _max/K _m ratio 7.4-fold higher for Cd²⁺ than for Cu²⁺ ions. Thus, although CtpG can accept different substrates in vitro, this P-type ATPase transports Cd²⁺ more efficiently than other heavy metal cations across the mycobacterial plasma membrane.