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Volume 155, Issue 5

Strain-specific impact of PsaR of on global gene expression and virulence Free

Abstract

Previous studies have indicated that PsaR of is a manganese-dependent regulator, negatively affecting the expression of at least seven genes. Here, we extended these observations by transcriptome and proteome analysis of mutants in strains D39 and TIGR4. The microarray analysis identified three shared PsaR targets: the operon, and . In addition, we found 31 genes to be regulated by PsaR in D39 only, most strikingly a cellobiose-specific phosphotransferase system (PTS) and a putative bacteriocin operon (). In TIGR4, 14 PsaR gene targets were detected, with the pathogenicity islet being the most pronounced. Proteomics confirmed most of the shared gene targets. To examine the contribution of PsaR to pneumococcal virulence, we compared D39 and TIGR4 wild-type (wt) and mutants in three murine infection models. During colonization, no clear effect was observed of the mutation in either D39 or TIGR4. In the pneumonia model, small but significant differences were observed in the lungs of mice infected with either D39wt or Δ: D39Δ had an initial advantage in survival in the lungs. Conversely, TIGR4Δ-infected mice had significantly lower bacterial loads at 24 h only. Finally, during experimental bacteraemia, D39Δ-infected mice had significantly lower bacterial loads in the bloodstream than wt-infected mice for the first 24 h of infection. TIGR4Δ showed attenuation at 36 h only. In conclusion, our results show that PsaR of D39 and TIGR4 has a strain-specific role in global gene expression and in the development of bacteraemia in mice.

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  • Accepted:
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Keyword(s): CSP, competence-stimulating pepide , PTS, phosphotransferase system and SILAC, stable isotope labelling in cell culture
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2009-05-01
2024-04-19
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References

  1. Adrian P. V., Thomson C. J., Klugman K. P., Amyes S. G. 2000; New gene cassettes for trimethoprim resistance, dfr13 , and streptomycin-spectinomycin resistance, aadA4 , inserted on a class 1 integron. Antimicrob Agents Chemother 44:355–361
     [Google Scholar]
  2. Anderton J. M., Rajam G., Romero-Steiner S., Summer S., Kowalczyk A. P., Carlone G. M., Sampson J. S., Ades E. W. 2007; E-cadherin is a receptor for the common protein pneumococcal surface adhesin A (PsaA) of Streptococcus pneumoniae . Microb Pathog 42:225–236
     [Google Scholar]
  3. Archibald F. S., Fridovich I. 1981; Manganese, superoxide dismutase, and oxygen tolerance in some lactic acid bacteria. J Bacteriol 146:928–936
     [Google Scholar]
  4. Blue C. E., Mitchell T. J. 2003; Contribution of a response regulator to the virulence of Streptococcus pneumoniae is strain dependent. Infect Immun 71:4405–4413
     [Google Scholar]
  5. Bogaert D., De Groot R., Hermans P. W. 2004; Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis 4:144–154
     [Google Scholar]
  6. Briles D. E., Ades E., Paton J. C., Sampson J. S., Carlone G. M., Huebner R. C., Virolainen A., Swiatlo E., Hollingshead S. K. 2000; Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae . Infect Immun 68:796–800
     [Google Scholar]
  7. Chapuy-Regaud S., Ogunniyi A. D., Diallo N., Huet Y., Desnottes J. F., Paton J. C., Escaich S., Trombe M. C. 2003; RegR, a global LacI/GalR family regulator, modulates virulence and competence in Streptococcus pneumoniae . Infect Immun 71:2615–2625
     [Google Scholar]
  8. Chastanet A., Prudhomme M., Claverys J. P., Msadek T. 2001; Regulation of Streptococcus pneumoniae clp genes and their role in competence development and stress survival. J Bacteriol 183:7295–7307
     [Google Scholar]
  9. Chicharro J. L., Serrano V., Urena R., Gutierrez A. M., Carvajal A., Fernandez-Hernando P., Lucia A. 1999; Trace elements and electrolytes in human resting mixed saliva after exercise. Br J Sports Med 33:204–207
     [Google Scholar]
  10. Dawid S., Roche A. M., Weiser J. N. 2007; The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivo . Infect Immun 75:443–451
     [Google Scholar]
  11. de Saizieu A., Gardes C., Flint N., Wagner C., Kamber M., Mitchell T. J., Keck W., Amrein K. E., Lange R. 2000; Microarray-based identification of a novel Streptococcus pneumoniae regulon controlled by an autoinduced peptide. J Bacteriol 182:4696–4703
     [Google Scholar]
  12. Dintilhac A., Alloing G., Granadel C., Claverys J. P. 1997; Competence and virulence of Streptococcus pneumoniae : Adc and PsaA mutants exhibit a requirement for Zn and Mn resulting from inactivation of putative ABC metal permeases. Mol Microbiol 25:727–739
     [Google Scholar]
  13. Garcia de la Nava J., van Hijum S., Trelles O. 2003; PreP: gene expression data pre-processing. Bioinformatics 19:2328–2329
     [Google Scholar]
  14. Giammarinaro P., Paton J. C. 2002; Role of RegM, a homologue of the catabolite repressor protein CcpA, in the virulence of Streptococcus pneumoniae . Infect Immun 70:5454–5461
     [Google Scholar]
  15. Glover D. T., Hollingshead S. K., Briles D. E. 2008; Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis. Infect Immun 76:2767–2776
     [Google Scholar]
  16. Hakenbeck R., Balmelle N., Weber B., Gardes C., Keck W., de Saizieu A. 2001; Mosaic genes and mosaic chromosomes: intra- and interspecies genomic variation of Streptococcus pneumoniae . Infect Immun 69:2477–2486
     [Google Scholar]
  17. Hanks T. S., Liu M., McClure M. J., Fukumura M., Duffy A., Lei B. 2006; Differential regulation of iron- and manganese-specific MtsABC and heme-specific HtsABC transporters by the metalloregulator MtsR of group A Streptococcus . Infect Immun 74:5132–5139
     [Google Scholar]
  18. Hava D. L., Camilli A. 2002; Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol Microbiol 45:1389–1406
     [Google Scholar]
  19. Hava D. L., Hemsley C. J., Camilli A. 2003a; Transcriptional regulation in the Streptococcus pneumoniae rlrA pathogenicity islet by RlrA. J Bacteriol 185:413–421
     [Google Scholar]
  20. Hava D. L., LeMieux J., Camilli A. 2003b; From nose to lung: the regulation behind Streptococcus pneumoniae virulence factors. Mol Microbiol 50:1103–1110
     [Google Scholar]
  21. Hemsley C., Joyce E., Hava D. L., Kawale A., Camilli A. 2003; MgrA, an orthologue of Mga, acts as a transcriptional repressor of the genes within the rlrA pathogenicity islet in Streptococcus pneumoniae . J Bacteriol 185:6640–6647
     [Google Scholar]
  22. Hendriksen W. T., Silva N., Bootsma H. J., Blue C. E., Paterson G. K., Kerr A. R., de Jong A., Kuipers O. P., Hermans P. W., Mitchell T. J. 2007; Regulation of gene expression in Streptococcus pneumoniae by response regulator 09 is strain dependent. J Bacteriol 189:1382–1389
     [Google Scholar]
  23. Hendriksen W. T., Bootsma H. J., Estevao S., Hoogenboezem T., de Jong A., de Groot R., Kuipers O. P., Hermans P. W. 2008a; CodY of Streptococcus pneumoniae : link between nutritional gene regulation and colonization. J Bacteriol 190:590–601
     [Google Scholar]
  24. Hendriksen W. T., Kloosterman T. G., Bootsma H. J., Estevao S., de Groot R., Kuipers O. P., Hermans P. W. 2008b; Site-specific contributions of glutamine-dependent regulator GlnR and GlnR-regulated genes to virulence of Streptococcus pneumoniae . Infect Immun 76:1230–1238
     [Google Scholar]
  25. Ibrahim Y. M., Kerr A. R., Silva N. A., Mitchell T. J. 2005; Contribution of the ATP-dependent protease ClpCP to the autolysis and virulence of Streptococcus pneumoniae . Infect Immun 73:730–740
     [Google Scholar]
  26. Jakubovics N. S., Jenkinson H. F. 2001; Out of the iron age: new insights into the critical role of manganese homeostasis in bacteria. Microbiology 147:1709–1718
     [Google Scholar]
  27. Jakubovics N. S., Smith A. W., Jenkinson H. F. 2000; Expression of the virulence-related Sca (Mn2+) permease in Streptococcus gordonii is regulated by a diphtheria toxin metallorepressor-like protein ScaR. Mol Microbiol 38:140–153
     [Google Scholar]
  28. Johnston J. W., Myers L. E., Ochs M. M., Benjamin W. H. Jr, Briles D. E., Hollingshead S. K. 2004; Lipoprotein PsaA in virulence of Streptococcus pneumoniae : surface accessibility and role in protection from superoxide. Infect Immun 72:5858–5867
     [Google Scholar]
  29. Johnston J. W., Briles D. E., Myers L. E., Hollingshead S. K. 2006; Mn2+-dependent regulation of multiple genes in Streptococcus pneumoniae through PsaR and the resultant impact on virulence. Infect Immun 74:1171–1180
     [Google Scholar]
  30. Kadioglu A., Gingles N. A., Grattan K., Kerr A., Mitchell T. J., Andrew P. W. 2000; Host cellular immune response to pneumococcal lung infection in mice. Infect Immun 68:492–501
     [Google Scholar]
  31. Kerr A. R., Adrian P. V., Estevao S., de Groot R., Alloing G., Claverys J. P., Mitchell T. J., Hermans P. W. 2004; The Ami-AliA/AliB permease of Streptococcus pneumoniae is involved in nasopharyngeal colonization but not in invasive disease. Infect Immun 72:3902–3906
     [Google Scholar]
  32. Kloosterman T. G., Hendriksen W. T., Bijlsma J. J., Bootsma H. J., van Hijum S. A., Kok J., Hermans P. W., Kuipers O. P. 2006; Regulation of glutamine and glutamate metabolism by GlnR and GlnA in Streptococcus pneumoniae . J Biol Chem 281:25097–25109
     [Google Scholar]
  33. Kloosterman T. G., van der Kooi-Pol M. M., Bijlsma J. J., Kuipers O. P. 2007; The novel transcriptional regulator SczA mediates protection against Zn2+ stress by activation of the Zn2+-resistance gene czcD in Streptococcus pneumoniae . Mol Microbiol 65:1049–1063
     [Google Scholar]
  34. Kloosterman T. G., Witwicki R. M., van der Kooi-Pol M. M., Bijlsma J. J., Kuipers O. P. 2008; Opposite effects of Mn2+ and Zn2+ on the PsaR-mediated expression of the virulence genes pcpA, prtA and psaBCA of Streptococcus pneumoniae . J Bacteriol 190:5382–5393
     [Google Scholar]
  35. Lanie J. A., Ng W. L., Kazmierczak K. M., Andrzejewski T. M., Davidsen T. M., Wayne K. J., Tettelin H., Glass J. I., Winkler M. E. 2007; Genome sequence of Avery's virulent serotype 2 strain D39 of Streptococcus pneumoniae and comparison with that of unencapsulated laboratory strain R6. J Bacteriol 189:38–51
     [Google Scholar]
  36. Lau G. W., Haataja S., Lonetto M., Kensit S. E., Marra A., Bryant A. P., McDevitt D., Morrison D. A., Holden D. W. 2001; A functional genomic analysis of type 3 Streptococcus pneumoniae virulence. Mol Microbiol 40:555–571
     [Google Scholar]
  37. Lawrence M. C., Pilling P. A., Epa V. C., Berry A. M., Ogunniyi A. D., Paton J. C. 1998; The crystal structure of pneumococcal surface antigen PsaA reveals a metal-binding site and a novel structure for a putative ABC-type binding protein. Structure 6:1553–1561
     [Google Scholar]
  38. Long A. D., Mangalam H. J., Chan B. Y., Tolleri L., Hatfield G. W., Baldi P. 2001; Improved statistical inference from DNA microarray data using analysis of variance and a Bayesian statistical framework. Analysis of global gene expression in Escherichia coli K12. J Biol Chem 276:19937–19944
     [Google Scholar]
  39. McAllister L. J., Tseng H. J., Ogunniyi A. D., Jennings M. P., McEwan A. G., Paton J. C. 2004; Molecular analysis of the psa permease complex of Streptococcus pneumoniae . Mol Microbiol 53:889–901
     [Google Scholar]
  40. McCluskey J., Hinds J., Husain S., Witney A., Mitchell T. J. 2004; A two-component system that controls the expression of pneumococcal surface antigen A (PsaA) and regulates virulence and resistance to oxidative stress in Streptococcus pneumoniae . Mol Microbiol 51:1661–1675
     [Google Scholar]
  41. Paik S., Brown A., Munro C. L., Cornelissen C. N., Kitten T. 2003; The sloABCR operon of Streptococcus mutans encodes an Mn and Fe transport system required for endocarditis virulence and its Mn-dependent repressor. J Bacteriol 185:5967–5975
     [Google Scholar]
  42. Paterson G. K., Blue C. E., Mitchell T. J. 2006; An operon in Streptococcus pneumoniae containing a putative alkylhydroperoxidase D homologue contributes to virulence and the response to oxidative stress. Microb Pathog 40:152–160
     [Google Scholar]
  43. Polissi A., Pontiggia A., Feger G., Altieri M., Mottl H., Ferrari L., Simon D. 1998; Large-scale identification of virulence genes from Streptococcus pneumoniae . Infect Immun 66:5620–5629
     [Google Scholar]
  44. Romero-Steiner S., Pilishvili T., Sampson J. S., Johnson S. E., Stinson A., Carlone G. M., Ades E. W. 2003; Inhibition of pneumococcal adherence to human nasopharyngeal epithelial cells by anti-PsaA antibodies. Clin Diagn Lab Immunol 10:246–251
     [Google Scholar]
  45. Romero-Steiner S., Caba J., Rajam G., Langley T., Floyd A., Johnson S. E., Sampson J. S., Carlone G. M., Ades E. 2006; Adherence of recombinant pneumococcal surface adhesin A (rPsaA)-coated particles to human nasopharyngeal epithelial cells for the evaluation of anti-PsaA functional antibodies. Vaccine 24:3224–3231
     [Google Scholar]
  46. Sanchez-Beato A. R., Lopez R., Garcia J. L. 1998; Molecular characterization of PcpA: a novel choline-binding protein of Streptococcus pneumoniae . FEMS Microbiol Lett 164:207–214
     [Google Scholar]
  47. Talkington D. F., Brown B. G., Tharpe J. A., Koenig A., Russell H. 1996; Protection of mice against fatal pneumococcal challenge by immunization with pneumococcal surface adhesin A (PsaA. Microb Pathog 21:17–22
     [Google Scholar]
  48. Tseng H. J., McEwan A. G., Paton J. C., Jennings M. P. 2002; Virulence of Streptococcus pneumoniae : PsaA mutants are hypersensitive to oxidative stress. Infect Immun 70:1635–1639
     [Google Scholar]
  49. van Hijum S. A., Garcia de la Nava J., Trelles O., Kok J., Kuipers O. P. 2003; MicroPreP: a cDNA microarray data pre-processing framework. Appl Bioinformatics 2:241–244
     [Google Scholar]
  50. Varrot A., Yamamoto H., Sekiguchi J., Thompson J., Davies G. J. 1999; Crystallization and preliminary X-ray analysis of the 6-phospho-alpha-glucosidase from Bacillus subtilis . Acta Crystallogr D Biol Crystallogr 55:1212–1214
     [Google Scholar]
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Strain-specific impact of PsaR of Streptococcus pneumoniae on global gene expression and virulence
Microbiology 155, 1569 (2009); https://doi.org/10.1099/mic.0.025072-0
/content/journal/micro/10.1099/mic.0.025072-0
/content/journal/micro/10.1099/mic.0.025072-0
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