Opposite effects of Mn2+ and Zn2+ on PsaR-mediated expression of the virulence genes pcpA, prtA, and psaBCA of Streptococcus pneumoniae.
Homeostasis of Zn(2+) and Mn(2+) is important for the physiology and virulence of the human pathogen Streptococcus pneumoniae. Here, transcriptome analysis was used to determine the response of S. pneumoniae D39 to a high concentration of Zn(2+). Interestingly, virulence genes encoding the choline binding protein PcpA, the extracellular serine protease PrtA, and the Mn(2+) uptake system PsaBC(A) were strongly upregulated in the presence of Zn(2+). Using random mutagenesis, a previously described Mn(2+)-responsive transcriptional repressor, PsaR, was found to mediate the observed Zn(2+)-dependent derepression. In addition, PsaR is also responsible for the Mn(2+)-dependent repression of these genes. Subsequently, we investigated how these opposite effects are mediated by the same regulator. In vitro binding of purified PsaR to the prtA, pcpA, and psaB promoters was stimulated by Mn(2+), whereas Zn(2+) destroyed the interaction of PsaR with its target promoters. Mutational analysis of the pcpA promoter demonstrated the presence of a PsaR operator that mediates the transcriptional effects. In conclusion, PsaR is responsible for the counteracting effects of Mn(2+) and Zn(2+) on the expression of several virulence genes in S. pneumoniae, suggesting that the ratio of these metal ions exerts an important influence on pneumococcal pathogenesis.
Kloosterman
Tomas G
TG
Department of Molecular Genetics, University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, PO Box 14, 9750 AA Haren, The Netherlands.
Witwicki
Robert M
RM
van der Kooi-Pol
Magdalena M
MM
Bijlsma
Jetta J E
JJ
Kuipers
Oscar P
OP
D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002413:Cations, Divalent / Q000378:metabolism; D004251:DNA Transposable Elements; D004269:DNA, Bacterial / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D006801:Humans; D008345:Manganese / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis; D009875:Operator Regions, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000502:physiology*; D037521:Virulence Factors / Q000096:biosynthesis*; D015032:Zinc / Q000378:metabolism*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D001426:Bacterial Proteins; D002413:Cations, Divalent; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D037521:Virulence Factors; D008345:Manganese; D001616:beta-Galactosidase; D015032:Zinc