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

P1B-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 P1B-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 P1B-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 Vmax/Km 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.