1887

Abstract

The temperature can vary according to the host tissue and the response to infection. has evolved mechanisms to survive these temperature differences, but neither the consequences of different temperatures for pneumococcal phenotype nor the genetic basis of thermal adaptation are known in detail. In our previous study [ 16 ], we found that CiaR, which is a part of two-component regulatory system CiaRH, as well as 17 genes known to be controlled by CiaRH, were identified to be differentially expressed with temperature. One of the CiaRH-regulated genes shown to be differentially regulated by temperature is for the high-temperature requirement protein (HtrA), coded by SPD_2068 (). In this study, we hypothesized that the CiaRH system plays an important role in pneumococcal thermal adaptation through its control over . This hypothesis was evaluated by testing strains mutated or overexpressing and/or , in and assays. The results showed that in the absence of , the growth, haemolytic activity, amount of capsule and biofilm formation were considerably diminished at 40 °C only, while the cell size and virulence were affected at both 34 and 40 °C. The overexpression of in the ∆ background reconstituted the growth at all temperatures, and the haemolytic activity, biofilm formation and virulence of ∆ partially at 40 °C. We also showed that overexpression of in the wild-type promoted pneumococcal virulence at 40 °C, while the increase of capsule was observed at 34 °C, suggesting that the role of changes at different temperatures. Our data suggest that CiaR and HtrA play an important role in pneumococcal thermal adaptation.

Funding
This study was supported by the:
  • NIH (Award R01 AI135060-01A1)
    • Principle Award Recipient: HasanYesilkaya
  • NIH (Award R01 AI139077-01A1)
    • Principle Award Recipient: HasanYesilkaya
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-02-22
2024-11-10
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References

  1. Weiser JN, Ferreira DM, Paton JC. Streptococcus pneumoniae: transmission, colonization and invasion. Nat Rev Microbiol 2018; 16:355–367 [View Article]
    [Google Scholar]
  2. Alghofaili F, Najmuldeen H, Kareem BO, Shlla B, Fernandes VE et al. Host stress signals stimulate pneumococcal transition from colonization to dissemination into the lungs. mBio 2021; 12:e0256921 [View Article]
    [Google Scholar]
  3. Tóthpál A, Desobry K, Joshi SS, Wyllie AL, Weinberger DM. Variation of growth characteristics of pneumococcus with environmental conditions. BMC Microbiol 2019; 19:304 [View Article] [PubMed]
    [Google Scholar]
  4. Eichner H, Spelmink L, Pathak A, Henriques-Normark B, Loh E. Meningitis pathogens evade immune responses by thermosensing. bioRxiv 2019; 586131 [View Article]
    [Google Scholar]
  5. Pandya U, Allen CA, Watson DA, Niesel DW. Global profiling of Streptococcus pneumoniae gene expression at different growth temperatures. Gene 2005; 360:45–54 [View Article]
    [Google Scholar]
  6. Klinkert B, Narberhaus F. Microbial thermosensors. Cell Mol Life Sci 2009; 66:2661–2676 [View Article] [PubMed]
    [Google Scholar]
  7. Nguyen CT, Park SS, Rhee DK. Stress responses in Streptococcus species and their effects on the host. J Microbiol 2015; 53:741–749 [View Article]
    [Google Scholar]
  8. Roncarati D, Scarlato V. Regulation of heat-shock genes in bacteria: from signal sensing to gene expression output. FEMS Microbiol Rev 2017; 41:549–574 [View Article]
    [Google Scholar]
  9. Ojha A, Anand M, Bhatt A, Kremer L, Jacobs WR et al. GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria. Cell 2005; 123:861–873 [View Article] [PubMed]
    [Google Scholar]
  10. Klancnik A, Botteldoorn N, Herman L, Mozina SS. Survival and stress induced expression of groEL and rpoD of Campylobacter jejuni from different growth phases. Int J Food Microbiol 2006; 112:200–207 [View Article]
    [Google Scholar]
  11. Takaya A, Tomoyasu T, Matsui H, Yamamoto T. The DnaK/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is essential for invasion of epithelial cells and survival within macrophages, leading to systemic infection. Infect Immun 2004; 72:1364–1373 [View Article]
    [Google Scholar]
  12. Eichner H, Karlsson J, Spelmink L, Pathak A, Sham LT et al. RNA thermosensors facilitate Streptococcus pneumoniae and Haemophilus influenzae immune evasion. PLoS Pathog 2021; 17:e1009513 [View Article]
    [Google Scholar]
  13. Gazioglu O, Kareem BO, Afzal M, Shafeeq S, Kuipers OP et al. Glutamate Dehydrogenase (GdhA) of Streptococcus pneumoniae is required for high temperature adaptation. Infect Immun 2021; 89:e0040021 [View Article]
    [Google Scholar]
  14. Bhuiya MW, Sakuraba H, Ohshima T. Temperature dependence of kinetic parameters for hyperthermophilic glutamate dehydrogenase from Aeropyrum pernix K1. Biosci Biotechnol Biochem 2002; 66:873–876 [View Article]
    [Google Scholar]
  15. Lee YH, Kingston AW, Helmann JD. Glutamate dehydrogenase affects resistance to cell wall antibiotics in Bacillus subtilis. J Bacteriol 2012; 194:993–1001 [View Article]
    [Google Scholar]
  16. He LY, Le YJ, Guo Z, Li S, Yang XY. The role and regulatory network of the CiaRH two-component system in Streptococcal species. Front Microbiol 2021; 12:693858 [View Article]
    [Google Scholar]
  17. Dagkessamanskaia A, Moscoso M, Hénard V, Guiral S, Overweg K et al. Interconnection of competence, stress and CiaR regulons in Streptococcus pneumoniae: competence triggers stationary phase autolysis of ciaR mutant cells. Mol Microbiol 2004; 51:1071–1086 [View Article]
    [Google Scholar]
  18. Ibrahim YM, Kerr AR, McCluskey J, Mitchell TJ. Control of virulence by the two-component system CiaR/H is mediated via HtrA, a major virulence factor of Streptococcus pneumoniae. J Bacteriol 2004; 186:5258–5266 [View Article]
    [Google Scholar]
  19. Kochan TJ, Dawid S. The HtrA protease of Streptococcus pneumoniae controls density-dependent stimulation of the bacteriocin blp locus via disruption of pheromone secretion. J Bacteriol 2013; 195:1561–1572 [View Article]
    [Google Scholar]
  20. Mascher T, Heintz M, Zähner D, Merai M, Hakenbeck R. The CiaRH system of Streptococcus pneumoniae prevents lysis during stress induced by treatment with cell wall inhibitors and by mutations in pbp2x involved in beta-lactam resistance. J Bacteriol 2006; 188:1959–1968 [View Article]
    [Google Scholar]
  21. Mascher T, Zähner D, Merai M, Balmelle N, de Saizieu AB et al. The Streptococcus pneumoniae cia regulon: CiaR target sites and transcription profile analysis. J Bacteriol 2003; 185:60–70 [View Article]
    [Google Scholar]
  22. Blanchette-Cain K, Hinojosa CA, Akula Suresh Babu R, Lizcano A, Gonzalez-Juarbe N et al. Streptococcus pneumoniae biofilm formation is strain dependent, multifactorial, and associated with reduced invasiveness and immunoreactivity during colonization. mBio 2013; 4:e00745–13 [View Article]
    [Google Scholar]
  23. Hentrich K, Löfling J, Pathak A, Nizet V, Varki A et al. Streptococcus pneumoniae senses a human-like sialic acid profile via the response regulator CiaR. Cell Host Microbe 2016; 20:307–317 [View Article]
    [Google Scholar]
  24. Halfmann A, Kovács M, Hakenbeck R, Brückner R. Identification of the genes directly controlled by the response regulator CiaR in Streptococcus pneumoniae: five out of 15 promoters drive expression of small non-coding RNAs. Mol Microbiol 2007; 66:110–126 [View Article]
    [Google Scholar]
  25. Slager J, Aprianto R, Veening JW. Refining the pneumococcal competence regulon by RNA sequencing. J Bacteriol 2019; 201:13 [View Article]
    [Google Scholar]
  26. Patenge N, Pappesch R, Khani A, Kreikemeyer B. Genome-wide analyses of small non-coding RNAs in streptococci. Front Genet 2015; 6:189 [View Article]
    [Google Scholar]
  27. Chao Y, Bergenfelz C, Sun R, Han X, Achour A et al. The serine protease HtrA plays a key role in heat-induced dispersal of pneumococcal biofilms. Sci Rep 2020; 10:22455 [View Article] [PubMed]
    [Google Scholar]
  28. de Stoppelaar SF, Bootsma HJ, Zomer A, Roelofs JJTH, Hermans PWM et al. Streptococcus pneumoniae serine protease HtrA, but not SFP or PrtA, is a major virulence factor in pneumonia. PLoS One 2013; 8:e80062 [View Article]
    [Google Scholar]
  29. Peters K, Schweizer I, Hakenbeck R, Denapaite D. New insights into beta-lactam resistance of Streptococcus pneumoniae: serine protease HtrA degrades altered penicillin-binding protein 2x. Microorganisms 2021; 9:1685 [View Article]
    [Google Scholar]
  30. Sebert ME, Patel KP, Plotnick M, Weiser JN. Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling system. J Bacteriol 2005; 187:3969–3979 [View Article] [PubMed]
    [Google Scholar]
  31. Zhi X, Abdullah IT, Gazioglu O, Manzoor I, Shafeeq S et al. Rgg-Shp regulators are important for pneumococcal colonization and invasion through their effect on mannose utilization and capsule synthesis. Sci Rep 2018; 8:6369 [View Article] [PubMed]
    [Google Scholar]
  32. Al-Bayati FAY, Kahya HFH, Damianou A, Shafeeq S, Kuipers OP et al. Pneumococcal galactose catabolism is controlled by multiple regulators acting on pyruvate formate lyase. Sci Rep 2017; 7:43587 [View Article] [PubMed]
    [Google Scholar]
  33. Yesilkaya H, Kadioglu A, Gingles N, Alexander JE, Mitchell TJ et al. Role of manganese-containing superoxide dismutase in oxidative stress and virulence of Streptococcus pneumoniae. Infect Immun 2000; 68:2819–2826 [View Article]
    [Google Scholar]
  34. Feoktistova M, Geserick P, Leverkus M. Crystal violet assay for determining viability of cultured cells. Cold Spring Harb Protoc 2016; 2016:pdb.prot087379 [View Article]
    [Google Scholar]
  35. Marks LR, Davidson BA, Knight PR, Hakansson AP. Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. mBio 2013; 4:e00438-13 [View Article]
    [Google Scholar]
  36. Lim MS, Kim JA, Lim JG, Kim BS, Jeong KC et al. Identification and characterization of a novel serine protease, VvpS, that contains two functional domains and is essential for autolysis of Vibrio vulnificus. J Bacteriol 2011; 193:3722–3732 [View Article]
    [Google Scholar]
  37. Jabbour N, Lartigue MF. An inventory of CiaR-dependent small regulatory RNAs in Streptococci. Front Microbiol 2021; 12:669396 [View Article]
    [Google Scholar]
  38. Babbar A, Barrantes I, Pieper DH, Itzek A. Superantigen SpeA attenuates the biofilm forming capacity of Streptococcus pyogenes. J Microbiol 2019; 57:626–636 [View Article]
    [Google Scholar]
  39. Zhu B, Ge X, Stone V, Kong X, El-Rami F et al. ciaR impacts biofilm formation by regulating an arginine biosynthesis pathway in Streptococcus sanguinis SK36. Sci Rep 2017; 7:17183 [View Article]
    [Google Scholar]
  40. Trappetti C, Gualdi L, Di Meola L, Jain P, Korir CC et al. The impact of the competence quorum sensing system on Streptococcus pneumoniae biofilms varies depending on the experimental model. BMC Microbiol 2011; 11:75 [View Article]
    [Google Scholar]
  41. Cassone M, Gagne AL, Spruce LA, Seeholzer SH, Sebert ME. The HtrA protease from Streptococcus pneumoniae digests both denatured proteins and the competence-stimulating peptide. J Biol Chem 2012; 287:38449–38459 [View Article]
    [Google Scholar]
  42. Schnorpfeil A, Kranz M, Kovács M, Kirsch C, Gartmann J et al. Target evaluation of the non-coding csRNAs reveals a link of the two-component regulatory system CiaRH to competence control in Streptococcus pneumoniae R6. Mol Microbiol 2013; 89:334–349 [View Article]
    [Google Scholar]
  43. Giefing C, Jelencsics KE, Gelbmann D, Senn BM, Nagy E. The pneumococcal eukaryotic-type serine/threonine protein kinase StkP co-localizes with the cell division apparatus and interacts with FtsZ in vitro. Microbiol 2010; 156:1697–1707 [View Article]
    [Google Scholar]
  44. Echenique J, Kadioglu A, Romao S, Andrew PW, Trombe MC. Protein serine/threonine kinase StkP positively controls virulence and competence in Streptococcus pneumoniae. Infect Immun 2004; 72:2434–2437 [View Article]
    [Google Scholar]
  45. Fleurie A, Lesterlin C, Manuse S, Zhao C, Cluzel C et al. MapZ marks the division sites and positions FtsZ rings in Streptococcus pneumoniae. Nature 2014; 516:259–262 [View Article]
    [Google Scholar]
  46. Mitchell AM, Mitchell TJ. Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect 2010; 16:411–418 [View Article]
    [Google Scholar]
  47. Cho KH, Wang HS, Kim YK. Temperature-dependent hemolytic activity of membrane pore-forming peptide toxin, tolaasin. J Pept Sci 2010; 16:85–90 [View Article] [PubMed]
    [Google Scholar]
  48. Poole K, Braun V. Influence of growth temperature and lipopolysaccharide on hemolytic activity of Serratia marcescens. J Bacteriol 1988; 170:5146–5152 [View Article]
    [Google Scholar]
  49. Mowlds P, Kavanagh K. Effect of pre-incubation temperature on susceptibility of Galleria mellonella larvae to infection by Candida albicans. Mycopathologia 2008; 165:5–12 [View Article]
    [Google Scholar]
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