1887

Abstract

This study investigated the transcriptomic response of Streptococcus pneumoniae D39 to methionine. Transcriptome comparison of the S. pneumoniae D39 wild-type grown in chemically defined medium with 0–10 mM methionine revealed the elevated expression of various genes/operons involved in methionine synthesis and transport (fhs, folD, gshT, metA, metB-csd, metEF, metQ, tcyB, spd-0150, spd-0431 and spd-0618). Furthermore, β-galactosidase assays and quantitative RT-PCR studies demonstrated that the transcriptional regulator, CmhR (SPD-0588), acts as a transcriptional activator of the fhs, folD, metB-csd, metEF, metQ and spd-0431 genes. A putative regulatory site of CmhR was identified in the promoter region of CmhR-regulated genes and this CmhR site was further confirmed by promoter mutational experiments.

Keyword(s): CmhR , MetE , Methionine , MetQ and Pneumococcus
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000091
2016-10-01
2019-09-16
Loading full text...

Full text loading...

/deliver/fulltext/mgen/2/10/mgen000091.html?itemId=/content/journal/mgen/10.1099/mgen.0.000091&mimeType=html&fmt=ahah

References

  1. Afzal M., Shafeeq S., Kuipers O. P.. 2014; LacR is a repressor of lacABCD and LacT is an activator of lacTFEG, constituting the lac gene cluster in Streptococcus pneumoniae. Appl Environ Microbiol80:5349–5358 [CrossRef][PubMed]
    [Google Scholar]
  2. Afzal M., Manzoor I., Kuipers O. P.. 2015a; A fast and reliable pipeline for bacterial transcriptome analysis case study: serine-dependent gene regulation in Streptococcus pneumoniae. J Vis Exp
    [Google Scholar]
  3. Afzal M., Shafeeq S., Henriques-Normark B., Kuipers O. P.. 2015b; UlaR activates expression of the ula operon in Streptococcus pneumoniae in the presence of ascorbic acid. Microbiology161:41–49
    [Google Scholar]
  4. Baerends R. J., Smits W. K., de Jong A., Hamoen L. W., Kok J., Kuipers O. P.. 2004; Genome2D: a visualization tool for the rapid analysis of bacterial transcriptome data. Genome Biol5:R37 [CrossRef][PubMed]
    [Google Scholar]
  5. Bailey T. L., Elkan C.. 1994; Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol2:28–36
    [Google Scholar]
  6. Basavanna S., Chimalapati S., Maqbool A., Rubbo B., Yuste J., Wilson R. J., Hosie A., Ogunniyi A. D., Paton J. C. et al. 2013; The effects of methionine acquisition and synthesis on Streptococcus pneumoniae growth and virulence. PLoS One8:e49638 [CrossRef][PubMed]
    [Google Scholar]
  7. Cai X. Y., Maxon M. E., Redfield B., Glass R., Brot N., Weissbach H.. 1989; Methionine synthesis in Escherichia coli: effect of the MetR protein on metE and metH expression. Proc Natl Acad Sci U S A86:4407–4411 [CrossRef][PubMed]
    [Google Scholar]
  8. Cowan J. M., Urbanowski M. L., Talmi M., Stauffer G. V.. 1993; Regulation of the Salmonella typhimurium metF gene by the MetR protein. J Bacteriol175:5862–5866[PubMed]
    [Google Scholar]
  9. Darwin A. J.. 2005; Genome-wide screens to identify genes of human pathogenic Yersinia species that are expressed during host infection. Curr Issues Mol Biol7:135–149[PubMed]
    [Google Scholar]
  10. den Hengst C. D., Groeneveld M., Kuipers O. P., Kok J.. 2006; Identification and functional characterization of the Lactococcus lactis CodY-regulated branched-chain amino acid permease BcaP (CtrA). J Bacteriol188:3280–3289 [CrossRef][PubMed]
    [Google Scholar]
  11. Eisenreich W., Dandekar T., Heesemann J., Goebel W.. 2010; Carbon metabolism of intracellular bacterial pathogens and possible links to virulence. Nat Rev Microbiol8:401–412 [CrossRef][PubMed]
    [Google Scholar]
  12. Ejim L. J., D'Costa V. M., Elowe N. H., Loredo-Osti J. C., Malo D., Wright G. D.. 2004; Cystathionine beta-lyase is important for virulence of Salmonella enterica serovar typhimurium. Infect Immun72:3310–3314 [CrossRef][PubMed]
    [Google Scholar]
  13. Epshtein V., Mironov A. S., Nudler E.. 2003; The riboswitch-mediated control of sulfur metabolism in bacteria. Proc Natl Acad Sci U S A100:5052–5056 [CrossRef][PubMed]
    [Google Scholar]
  14. Fernández M., Kleerebezem M., Kuipers O. P., Siezen R. J., van Kranenburg R.. 2002; Regulation of the metC-cysK operon, involved in sulfur metabolism in Lactococcus lactis. J Bacteriol184:82–90 [CrossRef][PubMed]
    [Google Scholar]
  15. Fontecave M., Atta M., Mulliez E.. 2004; S-adenosylmethionine: nothing goes to waste. Trends Biochem Sci29:243–249 [CrossRef][PubMed]
    [Google Scholar]
  16. Fuchs R. T., Grundy F. J., Henkin T. M.. 2006; The S(MK) box is a new SAM-binding RNA for translational regulation of SAM synthetase. Nat Struct Mol Biol13:226–233 [CrossRef][PubMed]
    [Google Scholar]
  17. Gray B. M., Turner M. E., Dillon H. C.. 1982; Epidemiologic studies of Streptococcus pneumoniae in infants. the effects of season and age on pneumococcal acquisition and carriage in the first 24 months of life. Am J Epidemiol116:692–703[PubMed]
    [Google Scholar]
  18. Grundy F. J., Henkin T. M.. 2003; The T box and S box transcription termination control systems. Front Biosci J Virtual Libr8:d20–31
    [Google Scholar]
  19. Halfmann A., Hakenbeck R., Brückner R.. 2007; A new integrative reporter plasmid for Streptococcus pneumoniae. FEMS Microbiol Lett268:217–224 [CrossRef][PubMed]
    [Google Scholar]
  20. Hendriksen W. T., Bootsma H. J., Estevão S., Hoogenboezem T., de Jong A., de Groot R., Kuipers O. P., Hermans P. W.. 2008; CodY of Streptococcus pneumoniae: link between nutritional gene regulation and colonization. J Bacteriol190:590–601 [CrossRef][PubMed]
    [Google Scholar]
  21. Hill C. E., Metcalf D. S., MacInnes J. I.. 2003; A search for virulence genes of Haemophilus parasuis using differential display RT-PCR. Vet Microbiol96:189–202 [CrossRef][PubMed]
    [Google Scholar]
  22. Hullo M. F., Auger S., Dassa E., Danchin A., Martin-Verstraete I.. 2004; The metNPQ operon of Bacillus subtilis encodes an ABC permease transporting methionine sulfoxide, D- and L-methionine. Res Microbiol155:80–86 [CrossRef][PubMed]
    [Google Scholar]
  23. Ispahani P., Slack R. C., Donald F. E., Weston V. C., Rutter N.. 2004; Twenty year surveillance of invasive pneumococcal disease in Nottingham: serogroups responsible and implications for immunisation. Arch Dis Child89:757–762 [CrossRef][PubMed]
    [Google Scholar]
  24. Israelsen H., Madsen S. M., Vrang A., Hansen E. B., Johansen E.. 1995; Cloning and partial characterization of regulated promoters from Lactococcus lactis Tn917-lacZ integrants with the new promoter probe vector, pAK80. Appl Environ Microbiol61:2540–2547[PubMed]
    [Google Scholar]
  25. Kanehisa M., Goto S., Sato Y., Kawashima M., Furumichi M., Tanabe M.. 2014; Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res42:D199–205 [CrossRef][PubMed]
    [Google Scholar]
  26. Kilian M., Mestecky J., Schrohenloher R. E.. 1979; Pathogenic species of the genus Haemophilus and Streptococcus pneumoniae produce immunoglobulin A1 protease. Infect Immun26:143–149[PubMed]
    [Google Scholar]
  27. Kovaleva G. Y., Gelfand M. S.. 2007; Transcriptional regulation of the methionine and cysteine transport and metabolism in streptococci. FEMS Microbiol Lett276:207–215 [CrossRef][PubMed]
    [Google Scholar]
  28. 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 Bacteriol189:38–51 [CrossRef][PubMed]
    [Google Scholar]
  29. 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 Microbiol40:555–571 [CrossRef][PubMed]
    [Google Scholar]
  30. Lestrate P., Delrue R. M., Danese I., Didembourg C., Taminiau B., Mertens P., De Bolle X., Tibor A., Tang C. M., Letesson J. J.. 2000; Identification and characterization of in vivo attenuated mutants of Brucella melitensis. Mol Microbiol38:543–551 [CrossRef][PubMed]
    [Google Scholar]
  31. Maddocks S. E., Oyston P. C. F.. 2008; Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. Microbiology154:3609–3623 [CrossRef][PubMed]
    [Google Scholar]
  32. Mares R., Urbanowski M. L., Stauffer G. V.. 1992; Regulation of the Salmonella typhimurium metA gene by the metR protein and homocysteine. J Bacteriol174:390–397[PubMed]
    [Google Scholar]
  33. McDaniel B. A., Grundy F. J., Artsimovitch I., Henkin T. M.. 2003; Transcription termination control of the S box system: direct measurement of S-adenosylmethionine by the leader RNA. Proc Natl Acad Sci U S A100:3083–3088 [CrossRef][PubMed]
    [Google Scholar]
  34. Mei J. M., Nourbakhsh F., Ford C. W., Holden D. W.. 1997; Identification of Staphylococcus aureus virulence genes in a murine model of bacteraemia using signature-tagged mutagenesis. Mol Microbiol26:399–407 [CrossRef][PubMed]
    [Google Scholar]
  35. Merlin C., Gardiner G., Durand S., Masters M.. 2002; The Escherichia coli metD locus encodes an ABC transporter which includes Abc (MetN), YaeE (MetI), and YaeC (MetQ). J Bacteriol184:5513–5517 [CrossRef][PubMed]
    [Google Scholar]
  36. Neves A. R., Ventura R., Mansour N., Shearman C., Gasson M. J., Maycock C., Ramos A., Santos H.. 2002; Is the glycolytic flux in Lactococcus lactis primarily controlled by the redox charge? Kinetics of NAD(+) and NADH pools determined in vivo by 13C NMR. J Biol Chem277:28088–28098 [CrossRef][PubMed]
    [Google Scholar]
  37. O'Brien K. L., Wolfson L. J., Watt J. P., Henkle E., Deloria-Knoll M., McCall N., Lee E., Mulholland K., Levine O. S. et al. 2009; Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet374:893–902 [CrossRef][PubMed]
    [Google Scholar]
  38. Phillips N. J., John C. M., Reinders L. G., Gibson B. W., Apicella M. A., Griffiss J. M.. 1990; Structural models for the cell surface lipooligosaccharides of Neisseria gonorrhoeae and Haemophilus influenzae. Biomed Environ Mass Spectrom19:731–745 [CrossRef][PubMed]
    [Google Scholar]
  39. Ravanel S., Gakière B., Job D., Douce R.. 1998; The specific features of methionine biosynthesis and metabolism in plants. Proc Natl Acad Sci U S A95:7805–7812 [CrossRef][PubMed]
    [Google Scholar]
  40. Rodionov D. A., Vitreschak A. G., Mironov A. A., Gelfand M. S.. 2004; Comparative genomics of the methionine metabolism in gram-positive bacteria: a variety of regulatory systems. Nucleic Acids Res32:3340–3353 [CrossRef][PubMed]
    [Google Scholar]
  41. Saint-Girons I., Parsot C., Zakin M. M., Bârzu O., Cohen G. N.. 1988; Methionine biosynthesis in Enterobacteriaceae: biochemical, regulatory, and evolutionary aspects. CRC Crit Rev Biochem23:S1–42 [CrossRef][PubMed]
    [Google Scholar]
  42. Schell M. A.. 1993; Molecular biology of the LysR family of transcriptional regulators. Annu Rev Microbiol47:597–626 [CrossRef][PubMed]
    [Google Scholar]
  43. Schmittgen T. D., Livak K. J.. 2008; Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc3:1101–1108 [CrossRef][PubMed]
    [Google Scholar]
  44. Shafeeq S., Kloosterman T. G., Kuipers O. P.. 2011a; Transcriptional response of Streptococcus pneumoniae to Zn2+ limitation and the repressor/activator function of AdcR. Metallomics3:609–618 [CrossRef]
    [Google Scholar]
  45. Shafeeq S., Yesilkaya H., Kloosterman T. G., Narayanan G., Wandel M., Andrew P. W., Kuipers O. P., Morrissey J. A.. 2011b; The cop operon is required for copper homeostasis and contributes to virulence in Streptococcus pneumoniae. Mol Microbiol81:1255–1270 [CrossRef]
    [Google Scholar]
  46. Shafeeq S., Kloosterman T. G., Rajendran V., Kuipers O. P.. 2012; Characterization of the ROK-family transcriptional regulator RokA of Streptococcus pneumoniae D39. Microbiology158:2917–2926 [CrossRef][PubMed]
    [Google Scholar]
  47. Shafeeq S., Afzal M., Henriques-Normark B., Kuipers O. P.. 2015; Transcriptional profiling of UlaR-regulated genes in Streptococcus pneumoniae. Genom Data4:57–59 [CrossRef][PubMed]
    [Google Scholar]
  48. Shelver D., Rajagopal L., Harris T. O., Rubens C. E.. 2003; MtaR, a regulator of methionine transport, is critical for survival of group B Streptococcus in vivo. J Bacteriol185:6592–6599 [CrossRef][PubMed]
    [Google Scholar]
  49. Sperandio B., Polard P., Ehrlich D. S., Renault P., Guédon E.. 2005; Sulfur amino acid metabolism and its control in Lactococcus lactis IL1403. J Bacteriol187:3762–3778 [CrossRef][PubMed]
    [Google Scholar]
  50. Sperandio B., Gautier C., McGovern S., Ehrlich D. S., Renault P., Martin-Verstraete I., Guédon E.. 2007; Control of methionine synthesis and uptake by MetR and homocysteine in Streptococcus mutans. J Bacteriol189:7032–7044 [CrossRef][PubMed]
    [Google Scholar]
  51. Titgemeyer F., Hillen W.. 2002; Global control of sugar metabolism: a gram-positive solution. Antonie Van Leeuwenhoek82:59–71[PubMed]
    [Google Scholar]
  52. Weissbach H., Brot N.. 1991; Regulation of methionine synthesis in Escherichia coli. Mol Microbiol5:1593–1597 [CrossRef][PubMed]
    [Google Scholar]
  53. Winkler W. C., Nahvi A., Sudarsan N., Barrick J. E., Breaker R. R.. 2003; An mRNA structure that controls gene expression by binding S-adenosylmethionine. Nat Struct Biol10:701–707 [CrossRef][PubMed]
    [Google Scholar]
  54. Yesilkaya H., Manco S., Kadioglu A., Terra V. S., Andrew P. W.. 2008; The ability to utilize mucin affects the regulation of virulence gene expression in Streptococcus pneumoniae. FEMS Microbiol Lett278:231–235 [CrossRef][PubMed]
    [Google Scholar]
  55. Lanie, J. A., Ng, W. L., Kazmierczak, K. M., Andrzejewski, T. M., Davidsen, T. M., Wayne, K. J., Tettelin, H., Glass, J. I. and 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. NCBI Nucleotide sequence databasehttp://www.ncbi.nlm.nih.gov/nuccore/NC_008533.1
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000091
Loading
/content/journal/mgen/10.1099/mgen.0.000091
Loading

Data & Media loading...

Supplementary File 1

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error