The presence of these two genes was first suspected when Nelson and Kennedy (1972) showed that there were Mg-repressible and non-repressible Mg uptake systems in E. coli. The non-repressible uptake of Mg is mediated by the CorA protein. In S. typhimurium the repressible Mg uptake was eventually shown to be via the MgtA and MgtB proteins.
Both MgtA and MgtB are regulated by the PhoPQ system and are actively transcribed during the process of infection of human patients by S. typhimurium. Although neither gene is required for pathogenicity, the MgtB protein does enhance the long-term survival of the pathogen in the cell. The genes are also upregulated in vitro when the Mg concentration falls below 50 μM (Snavely et al., 1991a). Although the proteins have km values similar to CorA and transport rates approximately 10 times less, the genes may be part of a Mg scavenging system. Chamnongpol and Groisman (2002) presents evidence that the role of these proteins may be to compensate for the inactivation of the CorA protein by the PhoPQ regulon. The authors suggest that the CorA protein is inactivated to allow the avoidance of metal toxicity via the protein in the low Mg environments S. typhimurium is subjected to by cells after infection.
The proteins are both P-type ATPases
 and neither gene shows any similarity to CorA. The MgtA and MgtB proteins are 75% similar (50% identical), although it seems that MgtB may have been acquired by horizontal gene transfer as part of Salmonella Pathogenicity Island 3. The TM topology of the MgtB protein has been experimentally determined, showing that the protein has ten TM-spanning helices with the termini of the protein in the cytoplasm (see figure
). MgtA is present in widely divergent bacteria, but is not nearly as common as CorA, while MgtB appears to have a quite restricted distribution. No hypotheses for the unusual distribution have been suggested.
The figure, adapted from Smith et al. (1993b), shows the experimentally determined membrane topology of the MgtB protein in S. typhimurium. The TM domains are shown in light blue and the orientation in the membrane and the positions of the N- and C-termini are indicated. The figure is not drawn to scale.
While the MgtA and MgtB proteins are very similar, they do show some minor differences in activity. MgtB is very sensitive to temperature, losing all activity (with regard to Mg transport) at a temperature of 20 °C. Additionally, MgtB and MgtA are inhibited by different ranges of cations (Table A10.1).
The table lists cation transport characteristics of the MgtA and MgtB proteins in S. typhimurium as well as the kinetic data for the MgtA and MgtB transport proteins at 37 °C. The Vmax numbers listed in parentheses are those for uptake at 20 °C. The inhibition of Mg transport by Mn via MgtA showed unusual kinetics (see Figure 1 of Snavely et al., 1989b)
The MgtA and MgtB proteins are ATPases, using one molecule of ATP per transport cycle, whereas the Mg uptake via CorA is simply electrochemically favourable. Chamnongpol and Groisman (2002) have suggested that the MgtA and MgtB proteins form part of a metal toxicity avoidance system. Alternatively, as most P-type ATPases function as efflux mediating transporters, it has been suggested that the MgtA and MgtB proteins act as efflux proteins for a currently unidentified cation, and Mg transport is either non-specific or exchanged to maintain the electro-neutrality of the transport process. Further experiments will be required to define the physiological function of these proteins.