title: Interplay between manganese and zinc homeostasis in the human  pathogen Streptococcus pneumoniae.
abstract: 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 μM 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 μM 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.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, IN 47405-7102, USA.
authors.forename: Faith E
authors.initials: FE
authors.lastname: Jacobsen
authors.forename: Krystyna M
authors.initials: KM
authors.lastname: Kazmierczak
authors.forename: John P
authors.initials: JP
authors.lastname: Lisher
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Winkler
authors.forename: David P
authors.initials: DP
authors.lastname: Giedroc
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism; D003584:Cytological Techniques; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000502:physiology; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008345:Manganese / Q000378:metabolism*; D013058:Mass Spectrometry; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D015854:Up-Regulation; D015032:Zinc / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D004268:DNA-Binding Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; C085000:PsaA protein, Streptococcus; D012097:Repressor Proteins; D008345:Manganese; D004247:DNA; D015032:Zinc