Characterization of molecular determinants involved in magnesium homeostasis of Salmonella: Understanding the role of CorC protein

Magnesium is an essential divalent metal that serves many cellular functions in growing cells. Our recent data also point to the importance of magnesium in the fitness of quiescent cells (Metaane et al. 2022). Deletion of the rpoS gene, encoding the σS stress/stationary phase sigma subunit of RNA polymerase decreases by three-fold the Mg2+ content of Salmonella enterica serovar Typhimurium grown to stationary phase in nutrient-rich LB medium (ICPMS & chemical kit assay, Metaane et al. 2022 and 2023). The corA gene encoding the major Mg2+ transporter is activated by σS but the corA deletion does not affect the total Mg2+ content of the wild-type strain and rpoS deletion mutant suggesting that additional player(s) contribute(s) to Mg2+ homeostasis (Metaane et al. 2023). The other known Mg2+ transporters, MgtA and MgtB, are produced when bacteria faces very low Mg2+ concentration (Groisman et al 2021). Three additional genes (corB, corC and corD) may control Mg2+ efflux via CorA (Gibbons et al. 1991).

Our goal was to revisit molecular determinants involved in the control of magnesium homeostasis in quiescent S. Typhimurium. 

During the study of magnesium and cobalt transport by CorA in Salmonella, three loci named corB, corC and corD, involved in resistance to cobalt and magnesium efflux have been discovered by Gibson et al. (1991). It was proposed that CorB, CorC and CorD contribute to the efflux of divalent cations by CorA, either by coupling the transport of cations by CorA to an energy source, or as a cation sensor for the CorA protein. The corB, corC and corD genes have not been further characterized in Salmonella and their function remains unclear to date. We have identified the corB, corC and corD genes as corresponding to the yfjD, ybeX and possibly apaG genes, respectively, in Salmonella serovar Typhimurium strain ATCC14028. We have constructed deletions in these genes in order to study their physiological impact in Salmonella. In the present study, we report the characterization of the corC deletion mutant.

In other reports: 

• We describe the construction of corC, corB and corD mutants and their resistance phenotype towards cobalt, nickel and magnesium toxicity. NOREL Françoise, MONTEIL Véronique, & METAANE Selma. (2023). Towards new elements involved in magnesium and cobalt trafficking in Salmonella serovar Typhimurium. Zenodo. https://doi.org/10.5281/zenodo.8086417
• The bacterial two hybrid system (BACTH) was used to find out potential physical interactions between CorA, CorB(YfjD), CorC(YbeX) and ApaG.  NOREL F, METAANE S, & MONTEIL V. (2023). Detection of physical interactions between the magnesium transporter CorA and other Cor proteins using the bacterial two hybrid system (BACTH). Zenodo. https://doi.org/10.5281/zenodo.7994619
• Mass spectrometry proteomics was used to assess global effects of deletion of the corC gene on the Salmonella proteome. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD043903.

See also:

Phegnon, L., Uttenweiler-Joseph, S., & Létisse, F. (2024). EXTRAMETABOLOME ANALYSIS OF SALMONELLA corC MUTANTS BY NMR [Data set]. Zenodo. https://doi.org/10.5281/zenodo.10908203

This work was supported by the French National Research Agency (ANR-19-CE44-0005-01, PERIOMET project).

References

• Gibson MM, Bagga DA, Miller CG, Maguire ME. Magnesium transport in Salmonella typhimurium: the influence of new mutations conferring Co2+ resistance on the CorA Mg2+ transport system. Molecular microbiology. 1991;5(11):2753-62.
• Metaane S, Monteil V, Ayrault S, Bordier L, Levi-Meyreuis C, Norel F. The stress sigma factor sigmaS/RpoS counteracts Fur repression of genes involved in iron and manganese metabolism and modulates the ionome of Salmonella enterica serovar Typhimurium. PloS one. 2022;17(3):e0265511.
• Metaane S, Monteil V, Douché T, Giai Gianetto Q, Matondo M, Maufrais C, Norel F. Loss of CorA, the primary magnesium transporter of Salmonella, is alleviated by MgtA and PhoP-dependent compensatory mechanisms. PloS one. 2023;18(9):e0291736.
• Groisman EA, Duprey A, Choi J. How the PhoP/PhoQ System Controls Virulence and Mg(2+) Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution. Microbiology and molecular biology reviews: MMBR. 2021; 85(3):e0017620.