title: Deletion of a cation transporter promotes lysis in Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae is a significant human pathogen which causes respiratory and serious invasive diseases. Mg(2+) 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 Mg(2+) uptake of S. pneumoniae strain D39, a mutant was generated in SPD1383, a P-type ATPase with homology to the Salmonella Mg(2+) transporter MgtA, which has also been shown to be a Ca(2+) exporter in strain TIGR4. Under low-Ca(2+) conditions, mutation led to a growth defect in complex medium and the gene was nearly essential for growth under low-Mg(2+) conditions. Addition of Mg(2+) restored the normal growth of the mutant in all cases, but the addition of other divalent cations had no effect. Addition of Ca(2+), Mn(2+), and Zn(2+) in the presence of high Mg(2+) concentrations inhibited restoration of growth. The mutant was unable to proliferate in blood, which was also alleviated by the addition of Mg(2+). 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 Mg(2+) uptake and hypothesize that the protein is a Mg(2+/)Ca(2+) antiporter. Furthermore, a disturbance in Mg(2+) homeostasis seems to promote lysis of S. pneumoniae.
authors.affiliation: Department of Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, Rijksuniversiteit Groningen, Nijenborgh 7, 9747 AG Groningen, Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Neef
authors.forename: Vahid Farshchi
authors.initials: VF
authors.lastname: Andisi
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Oscar P
authors.initials: OP
authors.lastname: Kuipers
authors.forename: Jetta J E
authors.initials: JJ
authors.lastname: Bijlsma
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000382:microbiology; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013301:Streptolysins / Q000378:metabolism / Q000502:physiology; D015032:Zinc / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D000251:Adenosine Triphosphatases; C093585:MgtA protein, bacteria; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D015032:Zinc; D002118:Calcium