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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76965完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山(Jean-San Chia) | |
| dc.contributor.author | Guo-Wei Ku | en |
| dc.contributor.author | 顧國暐 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:41:49Z | - |
| dc.date.available | 2021-07-10T21:41:49Z | - |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-03 | |
| dc.identifier.citation | 1. Clarke, J.K., On the Bacterial Factor in the Ætiology of Dental Caries. British journal of experimental pathology, 1924. 5(3): p. 141-147. 2. Igarashi, T., A. Yamamoto, and N. Goto, Direct detection of Streptococcus mutans in human dental plaque by polymerase chain reaction. Oral microbiology and immunology, 1996. 11(5): p. 294-298. 3. McNeill, K. and I.R. Hamilton, Acid tolerance response of biofilm cells of Streptococcus mutans. FEMS Microbiology Letters, 2003. 221(1): p. 25-30. 4. Matsumoto-Nakano, M., Role of Streptococcus mutans surface proteins for biofilm formation. Jpn Dent Sci Rev, 2018. 54(1): p. 22-29. 5. Nakano, K., R. Nomura, and T. Ooshima, Streptococcus mutans and cardiovascular diseases. Japanese Dental Science Review, 2008. 44(1): p. 29-37. 6. Yumoto, H., et al., The Pathogenic Factors from Oral Streptococci for Systemic Diseases. Int J Mol Sci, 2019. 20(18). 7. Ann M. Stock, a. Victoria L. Robinson, and P.N. Goudreau, Two-Component Signal Transduction. Annual Review of Biochemistry, 2000. 69(1): p. 183-215. 8. Zschiedrich, C.P., V. Keidel, and H. Szurmant, Molecular Mechanisms of Two-Component Signal Transduction. J Mol Biol, 2016. 428(19): p. 3752-75. 9. Breland, E.J., A.R. Eberly, and M. Hadjifrangiskou, An Overview of Two-Component Signal Transduction Systems Implicated in Extra-Intestinal Pathogenic E. coli Infections. Front Cell Infect Microbiol, 2017. 7: p. 162. 10. West, A. H., Stock, A. M., Histidine kinases and response regulator proteins in two-component signaling systems. Trends in Biochemical Sciences, 26(6): p. 369–376. 11. Mitrophanov, A.Y. and E.A. Groisman, Signal integration in bacterial two-component regulatory systems. Genes Dev, 2008. 22(19): p. 2601-11. 12. Reinoso-Vizcaíno, N.M., et al., The pneumococcal two-component system VisRH is linked to enhanced intracellular survival of Streptococcus pneumoniaein influenza-infected pneumocytes. bioRxiv, 2019: p. 767855. 13. Biswas, I., et al., Involvement of sensor kinases in the stress tolerance response of Streptococcus mutans. J Bacteriol, 2008. 190(1): p. 68-77. 14. Li, Y.H., et al., Cell density modulates acid adaptation in Streptococcus mutans: implications for survival in biofilms. J Bacteriol, 2001. 183(23): p. 6875-84. 15. Desai, K., et al., Development of competence for genetic transformation of Streptococcus mutans in a chemically defined medium. J Bacteriol, 2012. 194(15): p. 3774-80. 16. Senadheera, M.D., et al., A VicRK signal transduction system in Streptococcus mutans affects gtfBCD, gbpB, and ftf expression, biofilm formation, and genetic competence development. J Bacteriol, 2005. 187(12): p. 4064-76. 17. Shankar, M., et al., Gene Regulation by the LiaSR Two-Component System in Streptococcus mutans. PLoS One, 2015. 10(5): p. e0128083. 18. Suntharalingam, P., et al., The LiaFSR system regulates the cell envelope stress response in Streptococcus mutans. J Bacteriol, 2009. 191(9): p. 2973-84. 19. Model, P., G. Jovanovic, and J. Dworkin, The Escherichia coli phage-shockprotein (psp) operon. Molecular Microbiology, 1997. 24(2): p. 255-261. 20. Darwin, A.J., The phage-shock-protein response. Mol Microbiol, 2005. 57(3): p. 621-8. 21. Rowley, G., et al., Pushing the envelope: extracytoplasmic stress responses in bacterial pathogens. Nat Rev Microbiol, 2006. 4(5): p. 383-94. 22. Flores-Kim, J. and A.J. Darwin, The Phage Shock Protein Response. Annu Rev Microbiol, 2016. 70: p. 83-101. 23. Flores-Kim, J. and A.J. Darwin, Phage shock protein C (PspC) of Yersinia enterocolitica is a polytopic membrane protein with implications for regulation of the Psp stress response. J Bacteriol, 2012. 194(23): p. 6548-59. 24. Srivastava, D., et al., Psp Stress Response Proteins Form a Complex with Mislocalized Secretins in the Yersinia enterocolitica Cytoplasmic Membrane. mBio, 2017. 8(5). 25. Darwin, A.J., Stress relief during host infection: The phage shock protein response supports bacterial virulence in various ways. PLoS Pathog, 2013. 9(7): p. e1003388. 26. Mansur, A.J., et al., Relapses, recurrences, valve replacements, and mortality during the long-term follow-up after infective endocarditis. Am Heart J, 2001. 141(1): p. 78-86. 27. Bayliss, R., et al., The microbiology and pathogenesis of infective endocarditis. British Heart Journal, 1983. 50(6): p. 513-519. 28. Thiene, G. and C. Basso, Pathology and pathogenesis of infective endocarditis in native heart valves. Cardiovasc Pathol, 2006. 15(5): p. 256-263. 29. Glaser, N., et al., Prosthetic Valve Endocarditis After Surgical Aortic Valve Replacement. Circulation, 2017. 136(3): p. 329-331. 30. Holland, T.L., et al., Infective endocarditis. Nat Rev Dis Primers, 2016. 2: p. 16059. 31. Mohiyiddeen, G., I. Brett, and E. Jude, Infective endocarditis caused by Staphylococcus aureus in a patient with atopic dermatitis: a case report. J Med Case Rep, 2008. 2: p. 143. 32. Birlutiu, V., R.M. Birlutiu, and V.S. Costache, Viridans streptococcal infective endocarditis associated with fixed orthodontic appliance managed surgically by mitral valve plasty: A case report. Medicine (Baltimore), 2018. 97(27): p. e11260. 33. Douglas, C.W.I., et al., Identity of viridans streptococci isolated from cases of infective endocarditis. Journal of Medical Microbiology, 1993. 39(3): p. 179-182. 34. Nomura, R., et al., Contribution of the interaction of Streptococcus mutans serotype k strains with fibrinogen to the pathogenicity of infective endocarditis. Infect Immun, 2014. 82(12): p. 5223-34. 35. Jung, C.J., et al., Platelets enhance biofilm formation and resistance of endocarditis-inducing streptococci on the injured heart valve. J Infect Dis, 2012. 205(7): p. 1066-75. 36. Donlan, R.M. and J.W. Costerton, Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev, 2002. 15(2): p. 167-93. 37. Flemming, H.C., et al., Biofilms: an emergent form of bacterial life. Nat Rev Microbiol, 2016. 14(9): p. 563-75. 38. Bowen, W.H. and H. Koo, Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms. Caries Res, 2011. 45(1): p. 69-86. 39. Okshevsky, M. and R.L. Meyer, The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Crit Rev Microbiol, 2015. 41(3): p. 341-52. 40. Jung, C.J., et al., AtlA Mediates Extracellular DNA Release, Which Contributes to Streptococcus mutans Biofilm Formation in an Experimental Rat Model of Infective Endocarditis. Infect Immun, 2017. 85(9). 41. Werdan, K., et al., Mechanisms of infective endocarditis: pathogen-host interaction and risk states. Nat Rev Cardiol, 2014. 11(1): p. 35-50. 42. Hangge, P., et al., Hemostasis and nanotechnology. Cardiovasc Diagn Ther, 2017. 7(Suppl 3): p. S267-S275. 43. Yeaman, M.R., Platelets: at the nexus of antimicrobial defence. Nat Rev Microbiol, 2014. 12(6): p. 426-37. 44. Fitzgerald, J.R., T.J. Foster, and D. Cox, The interaction of bacterial pathogens with platelets. Nat Rev Microbiol, 2006. 4(6): p. 445-57. 45. Shannon, O., et al., Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation. Mol Microbiol, 2007. 65(5): p. 1147-57. 46. Chia, J.S., et al., Platelet aggregation induced by serotype polysaccharides from Streptococcus mutans. Infect Immun, 2004. 72(5): p. 2605-17. 47. Roos, A., et al., Mini-review: A pivotal role for innate immunity in the clearance of apoptotic cells. Eur J Immunol, 2004. 34(4): p. 921-9. 48. Ricklin, D. and J.D. Lambris, Compstatin: A Complement Inhibitor on its Way to Clinical Application. Current Topics in Complement II, 2008. 632: p. 262-281. 49. Cvitkovitch, D.G., Y.H. Li, and R.P. Ellen, Quorum sensing and biofilm formation in Streptococcal infections. J Clin Invest, 2003. 112(11): p. 1626-32. 50. Jung, C.J., et al., Streptococcus mutans autolysin AtlA is a fibronectin-binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis. Mol Microbiol, 2009. 74(4): p. 888-902. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76965 | - |
| dc.description.abstract | 感染性心內膜炎是一種感染心血管系統並具有高復發率及致死率的的感染性疾病。人類口腔菌叢的轉糖鏈球菌是透過機會性感染引發感染性心內膜炎發生的主要致病菌之一。我們先前的成果指出，一種受LiaR調控的phage shock protein C相似蛋白在調控細菌於大鼠體內形成生物膜以造成感染性心內膜炎的能力中扮演重要角色；然而其中的機制並不清楚。在本篇研究中，我們發現phage shock protein C相似蛋白缺失突變株依賴胞外去氧核醣核酸以及依賴血小板形成體外生物膜的能力具有缺陷，其釋放胞外去氧核醣核酸及依靠纖維蛋白原的血小板結合能力也顯著變差。為了探討phage shock protein C相似蛋白的表現機制，血球凝集素標記的質體就此產生。人類血清迅速地刺激轉糖鏈球菌表現phage shock protein C相似蛋白，該刺激的效果呈現劑量效應且不需LiaSR雙分子系統的感應與調控。加熱去活化將使血清刺激phage shock protein C相似蛋白表現的能力變差，暗示著血清中負責進行調理作用的成分可能具有角色；然而抑制C3補體蛋白作用無法減少血清引起的phage shock protein C相似蛋白表現，於去除免疫球蛋白的血清中加入純化過的免疫球蛋白幾乎無法恢復血清的刺激效果，這些結果顯示C3補體蛋白和免疫球蛋白在血清引起的phage shock protein C相似蛋白表現中的角色並非最主要，可能有其他對溫度敏感的血清成分參與其中。總結而論，phage shock protein C相似蛋白是一種受人類血清刺激後所表現的蛋白，在轉糖鏈球菌引發之感染性心內膜炎致病機轉中調控細菌胞外去氧核醣核酸釋出、血小板黏附、生物膜形成。 | zh_TW |
| dc.description.abstract | Infective endocarditis (IE) is an infectious disease of cardiovascular system featuring high recurrence and mortality rate. Streptococcus mutans, an oral commensal flora, is the main cause of dental caries, and also one of the major opportunistic pathogens for IE. Our previous works indicated that phage shock protein C homolog protein (Pcp), a LiaR-regulated hypothetical protein of S. mutans, played important roles in modulating bacterial abilities to form biofilm in vivo for causing IE, but the mechanism remained unclear. In this study, we found that pcp-deficient mutant strain revealed defects in both of eDNA- and platelet-dependent biofilm formation in vitro. Pcp deficiency reduced the ability to release extracellular DNA and to bind the platelets in the fibrinogen-dependent manner. To investigate the mechanism of Pcp expression, the HA-tagged Pcp reporting plasmid was generated. Pcp expression was rapidly induced by human serum in a dose-dependent manner, which was independent of LiaSR sensing and regulation. Heat-inactivation of serum reduced the ability to induce Pcp expression, implying the role of serum opsonizing components. However, inhibition of complement C3 could not reduce and addition of purified IgG in Ig-depleted serum barely restored the serum-induced Pcp expression, suggesting the minor roles of IgG and C3 in serum-induced Pcp expression. These data indicated that other heat-sensitive serum component(s) is(are) involved in. Taken together, Pcp is a human serum-induced protein modulating bacterial eDNA release, platelet adhesion and biofilm formation in the pathogenesis of S. mutans-induced IE. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:41:49Z (GMT). No. of bitstreams: 1 U0001-0208202020432500.pdf: 2166871 bytes, checksum: 308986fb2eb881a89869068d5641506c (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝....I Abstract....II 中文摘要....IV Contents....V 圖目錄....VIII Chapter 1. Introduction....1 1.1 Streptococcus mutans (S. mutans)....1 1.2 Two-component regulatory system (TCS)....1 1.3 Phage shock protein response (Psp response)....3 1.4 Infective endocarditis (IE)....4 1.5 Biofilm....5 1.6 Interaction between pathogens and platelets....6 Chapter 2. Purpose and Specific Aim....7 Chapter 3. Materials and methods....8 3.1 Bacteria strains and growth conditions....8 3.2 In vitro growth measurement....9 3.3 In vitro biofilm and extracellular DNA (eDNA) quantification....9 3.4 Preparation of blood samples and platelet suspension....10 3.5 In vitro platelet aggregation....11 3.6 Strategies for bacteria stimulation and surface protein extraction....12 3.7 Serum IgG depletion and IgG purification....13 3.8 Western blotting (WB)....13 3.9 Enzyme-linked immunosorbent assay (ELISA)....14 3.10 Statistical analysis....15 Chapter 4. Results....16 4.1 Pcp modulates in vitro eDNA release and biofilm formation without drastically affecting bacterial growth....16 4.2 Pcp contributes to in vitro bacteria-platelet biofilm formation....17 4.3 Pcp is not required for initiating platelet activation and subsequent aggregation....17 4.4 Pcp contributes to platelet adherence facilitated by binding of fibrinogen....18 4.5 Strategy for targeting Pcp from surface protein fractions of S. mutans....18 4.6 Macromolecular serum components rapidly trigger Pcp expression in a dosedependnet manner....19 4.7 Serum-induced Pcp expression is independent of the signal transduction mediated by LiaS and LiaR....20 4.8 Heat-sensitive serum components are essential for the Pcp induction....21 4.9 Activation of C3 and subsequent complement proteins are not responsible for serum-induced Pcp expression....21 4.10 Serum components other than IgG are required for the Pcp induction....22 Chapter 5. Discussion....23 5.1 Further investigations are required to identify the pivotal serum components triggering Pcp induction....23 5.2 The involvement of other signal pathways in serum-induced Pcp expression need to be evaluated....25 5.3 The essential functions and characteristics of Pcp are required to be clarified....26 Chapter 6. References....27 Chapter 7. Figures....34 Chapter 8. Supplementary figures....50 | |
| dc.language.iso | en | |
| dc.subject | 胞外去氧核醣核酸 | zh_TW |
| dc.subject | 轉糖鏈球菌 | zh_TW |
| dc.subject | 感染性心內膜炎 | zh_TW |
| dc.subject | 生物膜 | zh_TW |
| dc.subject | phage shock protein C相似蛋白 | zh_TW |
| dc.subject | biofilm | en |
| dc.subject | Streptococcus mutans | en |
| dc.subject | phage shock protein C homolog protein (Pcp) | en |
| dc.subject | extracellular DNA (eDNA) | en |
| dc.subject | infective endocarditis | en |
| dc.title | 探討轉糖鏈球菌Phage Shock Protein C相似蛋白在感染性心內膜炎致病機轉中扮演的角色 | zh_TW |
| dc.title | The Role of Phage Shock Protein C Homolog Protein in the Pathogenesis of Streptococcus mutans-Induced Infective Endocarditis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 鍾筱菁(Chiau-Jing Jung) | |
| dc.contributor.oralexamcommittee | 林志萱(Jr-Shiuan Lin) | |
| dc.subject.keyword | 轉糖鏈球菌,感染性心內膜炎,生物膜,胞外去氧核醣核酸,phage shock protein C相似蛋白, | zh_TW |
| dc.subject.keyword | Streptococcus mutans,infective endocarditis,biofilm,extracellular DNA (eDNA),phage shock protein C homolog protein (Pcp), | en |
| dc.relation.page | 51 | |
| dc.identifier.doi | 10.6342/NTU202002225 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-08-04 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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