9.B.20 The Putative Mg²⁺ Transporter-C (MgtC) Family 

The MgtC protein of Salmonella typhimurium is encoded by a gene found upstream of the mgtB gene and probably within the same operon (mgtCBR) with it. The MgtB protein is known to be a Mg²⁺-transporting P-type ATPase (TC #3.A.3). It was suggested on the basis of gene proximity without direct experimental evidence that MgtC is an auxiliary protein for MgtB function. However, in Mycobacterium tuberculosis, a close MgtC homologue is found in a region of the genome that does not encode a comparable MgtB homologue. Moreover, loss of MgtC, due to an mgtC knock-out mutation, prevents growth of the bacteria at low Mg²⁺ concentrations (10-50 µM) under low pH conditions (pH 6.2 - 6.8). Growth was restored at higher concentrations of Mg²⁺ (100 µM) (Alix and Blanc-Potard, 2007). The results are consistent with a Mg²⁺ uniport or a Mg²⁺:H⁺ antiport mechanism, but a transport function for MgtC has not been established. MgtC (but not MgtB) is essential for virulence. Synthesis is regulated by MgtR and an antisense RNA termed AmgR (Lee and Groisman, 2010).  Roles of MgtC homologues in intramacrophage bacterial survival have been discussed (Alix and Blanc-Potard 2007).

The MgtC proteins of S. typhimurium and M. tuberculosis and the SapB protein of Bacillus subtilis exhibit 4-6 putative TMSs. Homologues are found in several bacteria including cyanobacteria, but not in archaea or eukaryotes. Most of these proteins are of a similar size, but a few are reported to be substantially smaller than the three proteins cited above. For example, SrpB of Synechococcus PCC7942, a cyanobacterial plasmid-encoded protein, which is transcriptionally induced by sulfur deprivation and controlled by the CysR protein, is 182 residues long. Some archaeal and bacterial homologues are large (400-600aas) and have 14 TMS in a 5+5+7 arrangement (see family proteins 9.B.20.3.1-3).

Günzel et al. (2006) have provided some characteristics of MgtC from Salmonella enterica. This protein is required for virulence in mice. They could not obtain evidence for a transport function, but noted that in eukaryotic cells, it activates the Na⁺, K⁺-ATPase. Moreover, Alix and Blanc-Potard (2007) summarized evidence that MgtC is required for the intramacrophage survival of several pathogens. They believe that this function may be unrelated to the ability of MgtC to promote survival at low Mg²⁺.

MgtC is required for intramacrophage replication of intracellular pathogens and growth in low Mg²⁺ medium. A link between these two phenotypes has been proposed due to putative Mg²⁺ deprivation inside the phagosome. MgtC is part of a family of proteins that share a conserved N-terminal transmembrane domain and a variable C-terminal domain. The Salmonella MgtC C-terminal domain is cytoplasmic, adopts a fold also found in metal transporters and RNA interacting domain, and does not bind Mg²⁺. MgtC homologues from diverse gamma-proteobacteria have been expressed in a Salmonella ΔmgtC strain. The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or P. aeruginosa MgtC complemented only in low Mg²⁺ medium, thus dissociating the two MgtC-related phenotypes.

MgtC is a dimer, bearing an ACT-like domain (Yang et al. 2012). A mutant lacking the mgtC gene exhibited increased cellulose levels due to increased expression of the cellulose synthase gene bcsA and of cyclic diguanylate, the allosteric activator of the BcsA protein (Pontes et al. 2015).

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