CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis

Abstract

Background: The intracellular concentration of heavy-metal cations, such as copper, nickel, and zinc is pivotal for the mycobacterial response to the hostile environment inside macrophages. To date, copper transport mediated by P-type ATPases across the mycobacterial plasma membrane has not been sufficiently explored. Results: In this work, the ATPase activity of the putative Mycobacterium tuberculosis P 1B-type ATPase CtpB was associated with copper (I) transport from mycobacterial cells. Although CtpB heterologously expressed in M. smegmatis induced tolerance to toxic concentrations of Cu 2+ and a metal preference for Cu + , the disruption of ctpB in M. tuberculosis cells did not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper. In addition, the Cu + ATPase activity of CtpB embedded in the plasma membrane showed features of high affinity/slow turnover ATPases, with enzymatic parameters K M 0.19 ± 0.04 µM and V max 2.29 ± 0.10 nmol/mg min. In contrast, the ctpB gene transcription was activated in cells under culture conditions that mimicked the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper. Conclusions: The overall results suggest that M. tuberculosis CtpB is associated with Cu + transport from mycobacterial cells possibly playing a role different from copper detoxification.

A Role for Mycobacterium tuberculosis Sigma Factor C in Copper Nutritional Immunity

“…The microarray results were confirmed by qRT-PCR of sigC , ctpB , and fadD10 ( rv0099 ) only ( Figure 2 B). The ctpB gene encodes a cytoplasmic membrane P 1B -type ATPase associated with transport of copper from mycobacterial cells [ 23 ]. Orthologs of genes in the ppe1–nrp operon are present in slow-growing pathogenic mycobacteria and in actinomyces [ 24 ].…”

Genome-wide Identification and Function Analysis of HMAD Gene Family in Cotton (Gossypium Spp.)

“…On the other hand, the transfer of heavy metals and salt stress are vacuole segregation [70,71], such as the P-type ATP as an important role, can not only balance the salt ions and also can balance of heavy metal ions [72][73][74][75] HMA genes can selectively absorb and transport metal ions [76]. CtpB, as a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis, is different from copper detoxi cation [77]. In Mycobacterium tuberculosis, Cu 2+ , Co 2+ , Ni 2+ , Zn 2+ , Cd 2+ and Pb 2+ stimulate the ATPase activity of the putative P1B-type ATPase CtpG in the plasma membrane, while Cd 2+ more e ciently than other heavy metal cations across the mycobacterial plasma membrane [78].…”

“…On the other hand, the transfer of heavy metals and salt stress are vacuole segregation [70,71], such as the P-type ATP as an important role, can not only balance the salt ions and also can balance of heavy metal ions [72][73][74][75] HMA genes can selectively absorb and transport metal ions [76]. CtpB, as a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis, is different from copper detoxi cation [77]. In [51].…”

Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms

“…The M. tuberculosis genome contains seven P 1B -ATPase-encoding genes, namely ctpA-ctpD, ctpG, ctpJ and ctpV. With the exception of CtpC, the substrates of the mycobacterial P 1B -ATPases are known from experimental evidence 20,[28][29][30][31][32] , or can be predicted from in silico analysis and the presence of conserved motifs [14][15][16]33,34 . CtpC was proposed to be an exporter of manganese in M. tuberculosis, albeit with an unusually low efficiency 35 .…”