Central role of manganese in regulation of stress responses, physiology, and metabolism in Streptococcus pneumoniae

J Bacteriol. 2010 Sep;192(17):4489-97. doi: 10.1128/JB.00064-10. Epub 2010 Jul 2.


The importance of Mn(2+) for pneumococcal physiology and virulence has been studied extensively. However, the specific cellular role(s) for which Mn(2+) is required are yet to be fully elucidated. Here, we analyzed the effect of Mn(2+) limitation on the transcriptome and proteome of Streptococcus pneumoniae D39. This was carried out by comparing a deletion mutant lacking the solute binding protein of the high-affinity Mn(2+) transporter, pneumococcal surface antigen A (PsaA), with its isogenic wild-type counterpart. We provide clear evidence for the Mn(2+)-dependent regulation of the expression of oxidative-stress-response enzymes SpxB and Mn(2+)-SodA and virulence-associated genes pcpA and prtA. We also demonstrate the upregulation of at least one oxidative- and nitrosative-stress-response gene cluster, comprising adhC, nmlR, and czcD, in response to Mn(2+) stress. A significant increase in 6-phosphogluconate dehydrogenase activity in the psaA mutant grown under Mn(2+)-replete conditions and upregulation of an oligopeptide ABC permease (AppDCBA) were also observed. Together, the results of transcriptomic and proteomic analyses provided evidence for Mn(2+) having a central role in activating or stimulating enzymes involved in central carbon and general metabolism. Our results also highlight the importance of high-affinity Mn(2+) transport by PsaA in pneumococcal competence, physiology, and metabolism and elucidate mechanisms underlying the response to Mn(2+) stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Culture Media
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial* / drug effects
  • Heat-Shock Response*
  • Lipoproteins / genetics
  • Lipoproteins / metabolism*
  • Manganese / metabolism*
  • Manganese / pharmacology
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress
  • Proteome
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / metabolism*
  • Streptococcus pneumoniae / physiology*


  • Adhesins, Bacterial
  • Bacterial Proteins
  • Culture Media
  • Lipoproteins
  • Proteome
  • PsaA protein, Streptococcus
  • Manganese