Bijlsma, “Deletion of a cation transporter promotes lysis

Streptococcus pneumoniae is a significant human pathogen which causes respiratory and serious invasive diseases. Mg2 is essential for life, and its concentration varies throughout the human body. Magnesium uptake plays an important role in the virulence of many bacterial pathogens. To study the Mg2 uptake of S. pneumoniae strain D39, a mutant was generated in SPD1383, a P-type ATPase with homology to the Salmonella Mg2 transporter MgtA, which has also been shown to be a Ca2 exporter in strain TIGR4. Under low-Ca2 conditions, mutation led to a growth defect in complex medium and the gene was nearly essential for growth under low-Mg2 conditions. Addition of Mg2 restored the normal growth of the mutant in all cases, but the addition of other divalent cations had no effect. Addition of Ca2, Mn2, and Zn2 in the presence of high Mg2 concentrations inhibited restoration of growth. The mutant was unable to proliferate in blood, which was also alleviated by the addition of Mg2. The protein was located in the membrane and produced in various S. pneumoniae strains and pathogenic streptococcal species. Surprisingly, mutation of the gene led to an elevated toxicity for endothelial cells. This was caused by an increased amount of pneumolysin in the medium, mediated by elevated lysis of the mutant. Thus, in this study, we uncovered a role for SPD1383 in Mg2 uptake and hypothesize that the protein is a Mg2/Ca2 antiporter. Furthermore, a disturbance in Mg2 homeostasis seems to promote lysis of S. pneumoniae