Interplay between manganese and zinc homeostasis in the human pathogen Streptococcus pneumoniae

ICP-MS analysis of Streptococcus pneumoniae reveals a high cell-associated Mn(II) concentration that is comparable to that of Zn(II). Stressing these cells with 100-200 mu M Zn(II) leads to a slow-growth phenotype and a total Mn(II) concentration that is reduced, with no decrease of other metal ions. Supplementation of the growth media with as little as 10 mu M Mn(II) fully restores the growth defect and cell-associated Mn(II) to normal levels. DNA microarray analysis reveals that zinc stress induces the expected upregulation of czcD (encoding a zinc effluxer), but also a pleiotropic transcriptional response suggestive of mild cell wall stress. Genes encoding a nitric oxide (NO) detoxification system (nmlR) and the Mn(II) uptake system (psaBCA) are also induced. We conclude that Zn(II) toxicity results in a cytoplasmic Mn(II) deficiency, possibly caused by competition at the Mn(II) uptake transporter protein PsaA.