Magnesium transport in Salmonella typhimurium:: regulation of mgtA and mgtCB during invasion of epithelial and macrophage cells

Salmonella typhimurium contains two inducible Mg2+ transport systems, MgtA and MgtB, the latter encoded by a two-gene operon, mgtCB. Mg2+ deprivation of S. typhimurium increases transcription of both mgtA and mgtCB over a thousandfold and a similar increase occurs upon S. typhimurium invasion of epithelial cells. These increases are mediated by the phoPQ two-component signal transduction system, an essential system for S. typhimurium virulence. It was therefore hypothesized that expression of MgtA and MgtCB is increased upon invasion of eukaryotic cells because of a lack of intravacuolar Mg2+. However, when S typhimurium was grown at pH 5.2. the capacity of the constitutive CorA transporter in mediating Mg2+ was greater than that: at pH 7.4. Furthermore, induction of mgtA and mgtCB transcription was greater in the presence of a wild-type corA allele than in its absence. This implies that intravacuolar 5 typhimurium could obtain sufficient Mg2+ via the CorA system. The effect of acid pH on mgtA and mgtCB transcription was also measured. Compared to induction at pH 7 4, exposure to pH 5 2 almost completely abolished induction of mgtA at low Mg2+ concentrations but diminished induction of mgtCB only twofold. Adaptation of cells to acid pH by overnight growth resulted in normal levels of induction of mgtA and mgtCB at low Mg2+ concentrations. These results imply an additional level of regulation for mgtA that is not present for mgtCB. Conversely, repression of mgtA and mgtCB expression by increased extracellular Mg2+ was relatively insensitive to acid. Transcription of both loci was strongly induced upon invasion of the Hep-2 or CMT-93 epithelial-like or J774 macrophage-like cell lines. However, the presence or absence of functional alleles of either or both mgtA or mgtCB had no effect on invasion efficiency or short-term survival of 5 typhimurium within the eukaryotic cells. It was concluded that the strong Mg2+-dependent induction of mgtA and mgtCB upon invasion of eukaryotic cells is not required because 5. typhimurium lacks sufficient Mg2+ during eukaryotic cell invasion and initial intravacuolar growth.