Co2+-dependent gene expression in Streptococcus pneumoniae: opposite effect of Mn2+ and Co2+ on the expression of the virulence genes psaBCA, pcpA, and prtA

Irfan Manzoor, Sulman Shafeeq, Tomas G. Kloosterman, Oscar P. Kuipers

Manganese (Mn(2+))-, zinc (Zn(2+))- and copper (Cu(2+)) play significant roles in transcriptional gene regulation, physiology, and virulence of Streptococcus pneumoniae. So far, the effect of the important transition metal ion cobalt (Co(2+)) on gene expression of S. pneumoniae has not yet been explored. Here, we study the impact of Co(2+) stress on the transcriptome of S. pneumoniae strain D39. BLAST searches revealed that the genome of S. pneumoniae encodes a putative Co(2+)-transport operon (cbi operon), the expression of which we show here to be induced by a high Co(2+) concentration. Furthermore, we found that Co(2+), as has been shown previously for Zn(2+), can cause derepression of the genes of the PsaR virulence regulon, encoding the Mn(2+)-uptake system PsaBCA, the choline binding protein PcpA and the cell-wall associated serine protease PrtA. Interestingly, although Mn(2+) represses expression of the PsaR regulon and Co(2+) leads to derepression, both metal ions stimulate interaction of PsaR with its target promoters. These data will be discussed in the light of previous studies on similar metal-responsive transcriptional regulators.