title: Central role of manganese in regulation of stress responses, physiology, and metabolism in Streptococcus pneumoniae.
abstract: 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.
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Abiodun D
authors.initials: AD
authors.lastname: Ogunniyi
authors.forename: Layla K
authors.initials: LK
authors.lastname: Mahdi
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
authors.forename: Christopher A
authors.initials: CA
authors.lastname: McDevitt
authors.forename: Mark B
authors.initials: MB
authors.lastname: Van der Hoek
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bagley
authors.forename: Peter
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Gould
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D015180:Electrophoresis, Gel, Two-Dimensional; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D018869:Heat-Shock Response; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D020543:Proteome; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D003470:Culture Media; D008074:Lipoproteins; D020543:Proteome; C085000:PsaA protein, Streptococcus; D008345:Manganese