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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 邱浩傑 | zh_TW |
| dc.contributor.advisor | Hao-Chieh Chiu | en |
| dc.contributor.author | 林翠嫻 | zh_TW |
| dc.contributor.author | Chui-Hian Lim | en |
| dc.date.accessioned | 2021-07-10T22:13:36Z | - |
| dc.date.available | 2024-02-28 | - |
| dc.date.copyright | 2018-10-11 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Kluytmans J, v.B.A., Verbrugh H., Nasal carriage of Staphylococcus aureus: Epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. , 1997 Jul. 10(3): p. 505-20.
2. FD, L., Staphylococcus aureus infections. . N Engl J Med. , 1998 Aug. 339(8): p. 520-32. 3. Cole, A.M., et al., Determinants of Staphylococcus aureus nasal carriage. Clin Diagn Lab Immunol, 2001. 8(6): p. 1064-9. 4. Cawdery, M., et al., The role of coagulase in the defence of Staphylococcus aureus against phagocytosis. Br J Exp Pathol, 1969. 50(4): p. 408-12. 5. Patel, A.H., et al., Virulence of protein A-deficient and alpha-toxin-deficient mutants of Staphylococcus aureus isolated by allele replacement. Infect Immun, 1987. 55(12): p. 3103-10. 6. Becker, K., et al., Prevalence of genes encoding pyrogenic toxin superantigens and exfoliative toxins among strains of Staphylococcus aureus isolated from blood and nasal specimens. J Clin Microbiol, 2003. 41(4): p. 1434-9. 7. BP, C., Staphylococcus aureus chronic and relapsing infections: Evidence of a role for persister cells: An investigation of persister cells, their formation and their role in S. aureus disease. Bioessays, 2014 Oct. 36(10): p. 991-6. 8. Tipper, D.J. and J.L. Strominger, Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci U S A, 1965. 54(4): p. 1133-41. 9. M., R., Resistances of Staphylococcus aureus to the action of penicillin. Proc Soc Exp Biol Med, 1942(51): p. 386-9. 10. Perez, F., R.A. Salata, and R.A. Bonomo, Current and novel antibiotics against resistant Gram-positive bacteria. Infection and drug resistance, 2008. 1: p. 27-44. 11. Organization, W.H., Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics, 2017: CBCnews. 12. Mohammad, H., Mayhoub, A. S., Cushman, M. & Seleem, M. N., Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci. . The Journal of antibiotics, 2015. 68: p. 259-266. 13. Organization, W.H., Global hepatitis report. 2017: p. 8-29. 14. Wang CC, L.W., Chu ML, Siu LK, Epidemiological typing of community-acquired methicillin-resistant Staphylococcus aureus isolates from children in Taiwan. Clin Infect Dis., 2004 Aug 39(4): p. 481-7. 15. Wang JT, C.Y., Yang TL, Chang SC, Molecular epidemiology and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in Taiwan. Diagn Microbiol Infect Dis., 2002 Mar. 42(3): p. 199-203. 16. Daum, R.S., Clinical practice. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med, 2007. 357(4): p. 380-90. 17. Madani TA, A.-A.N., Al-Sanousi AA, Ghabrah TM, Afandi SZ, Bajunid HA, Methicillin-resistant Staphylococcus aureus in two tertiary-care centers in Jeddah, Saudi Arabia. Infect Control Hosp Epidemiol., 2001 Apr. 22(4): p. 211-6. 18. A. R. Stacey, K.E.E., P. C. Chan, and R. R. Marples, An outbreak of methicillin resistant Staphylococcus aureus infection in a rugby football team. Br J Sports Med., 1998 Jun. 32(2): p. 153-4. 19. Hiramatsu, K., et al., The emergence and evolution of methicillin-resistant Staphylococcus aureus. Trends Microbiol, 2001. 9(10): p. 486-93. 20. Keane, C.T. and M.T. Cafferkey, Re-emergence of methicillin-resistant Staphylococcus aureus causing severe infection. J Infect, 1984. 9(1): p. 6-16. 21. Dowd, G., M. Cafferkey, and G. Dougan, Gentamicin and methicillin resistant Staphylococcus aureus in Dublin hospitals: molecular studies. J Med Microbiol, 1983. 16(2): p. 129-38. 22. David, M.Z. and R.S. Daum, Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev, 2010. 23(3): p. 616-87. 23. Boyle-Vavra, S. and R.S. Daum, Community-acquired methicillin-resistant Staphylococcus aureus: the role of Panton-Valentine leukocidin. Lab Invest, 2007. 87(1): p. 3-9. 24. Seybold, U., et al., Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis, 2006. 42(5): p. 647-56. 25. Lowy, F.D., Antimicrobial resistance: the example of Staphylococcus aureus. J Clin Invest, 2003. 111(9): p. 1265-73. 26. Soge, O.O., et al., A novel transposon, Tn6009, composed of a Tn916 element linked with a Staphylococcus aureus mer operon. J Antimicrob Chemother, 2008. 62(4): p. 674-80. 27. Liu, C., et al., Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children. Clinical Infectious Diseases, 2011. 52(3): p. e18-e55. 28. Hiramatsu, K., et al., Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother, 1997. 40(1): p. 135-6. 29. Limbago, B.M., et al., Report of the 13th Vancomycin-Resistant Staphylococcus aureus Isolate from the United States. Journal of Clinical Microbiology, 2014. 52(3): p. 998-1002. 30. Gu, B., et al., The emerging problem of linezolid-resistant Staphylococcus. J Antimicrob Chemother, 2013. 68(1): p. 4-11. 31. Baltz, R.H., Daptomycin: mechanisms of action and resistance, and biosynthetic engineering. Curr Opin Chem Biol, 2009. 13(2): p. 144-51. 32. Hetem, D.J. and M.J. Bonten, Clinical relevance of mupirocin resistance in Staphylococcus aureus. J Hosp Infect, 2013. 85(4): p. 249-56. 33. Cosgrove SE, S.G., Perencevich ENet al., Comparison of Mortality Associated with Methicillin-Resistant and MethicillinSusceptible Staphylococcus aureus Bacteremia: A Meta-analysis. Clin Infect Dis., 2003. 36(53-59). 34. Longzhu Cui, H.M., Kyoko Kuwahara-Arai, Hideaki Hanaki, and Keiichi Hiramatsu, Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50. Antimicrob Agents Chemother., 2000. 9: p. 2276-85. 35. Martins M, D.S., Fanning Set al., Potential role of non-antibiotics in the treatment of multidrug-resistant Gramnegative infections: mechanisms for their direct and indirect activities. Int J Antimicrob Agents, 2008. 31: p. 198–208. 36. Drug repositioning: auranofin as a prospective antimicrobial agent for the treatment of severe staphylococcal infections. Biometals., 2014. 27(4): p. 787-791. 37. Harbut, M.B.e.a., Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-redox homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 2015. 112: p. 4453–4458. 38. Leire Aguinagalde, R.D.e.-M.n., Jose Yuste, Inmaculada Royo, Carmen Gil, I´n˜igo Lasa,Mar Martı´n-Fontecha, Nagore Isabel Marı´n-Ramos, Carmen Ardanuy, Josefina Lin˜ares, Pedro Garcı´a, Ernesto Garcı´a and Jose´ M. Sa´nchez-Puelles, Auranofin efficacy against MDR Streptococcus pneumoniae and Staphylococcus aureus infections. J Antimicrob Chemother., 2015. 70(9): p. 2608-2617. 39. Hokai Y, J.B., Fernández-Gallardo J, Zakirkhodjaev N, Sanaú M, Muth TR, Contel M, Auranofin and related heterometallic gold(I)-thiolates as potent inhibitors of methicillin-resistant Staphylococcus aureus bacterial strains. J Inorg Biochem. ;. 2014 Sep. 138: p. 81-8. 40. Chang, H.C., et al., In vitro and in vivo activity of a novel sorafenib derivative SC5005 against MRSA. J Antimicrob Chemother, 2016. 71(2): p. 449-59. 41. CLSI, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, W. CLSI, PA, Editor 2007. 42. Tobias Do¨ rr, K.L., Marin Vulic´, SOS response induces persistence to fluoroquinolones in Escherichia coli. PLoS Genet. , 2009 Dec. 5(12): p. e1000760. 43. Won A, I.A., Interactions of antimicrobial peptide from C-terminus of myotoxin II with phospholipid mono- and bilayers. Biochim Biophys Acta., 2009 Oct. 1788(10): p. 2277-83. 44. Mishra NN, B.A., Correlation of cell membrane lipid profiles with daptomycin resistance in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. , 2013 Feb. 57(2): p. 1082-5. 45. Chen L, Y.H., Zhang G, Yao WM, Chen XZ, Zhang FC, Liang G, Autophagy inhibition contributes to the synergistic interaction between EGCG and doxorubicin to kill the hepatoma Hep3B cells. PLoS One. 21;9(1):e85771., 2014 Jan. 9(1): p. e85771. 46. Soica C, O.C., Borcan F, Danciu C, Trandafirescu C, Coricovac D, Crăiniceanu Z, Dehelean CA, Munteanu M, The synergistic biologic activity of oleanolic and ursolic acids in complex with hydroxypropyl-γ-cyclodextrin. Molecules, 2014 Apr. 19(5): p. 4924-40. 47. Mohammad Arjomandzadegan, M.S., Leonid Titov, Larissa Surkova, Hossein Sarmadian, Reza Ghasemikhah, and Hossein Hosseiny, Transmission electron microscopy of XDR Mycobacterium tuberculosis isolates grown on high dose of ofloxacin. Sci Pharm., 2017. 85(1): p. 3. 48. Snel, K.-E.Y.a.J., Transmission electron microscopic demonstration of phagocytosis and intracellular processing of segmented filamentous bacteria by intestinal epithelial cells of the chick ileum. Infect Immun., 2000 Nov. 68(11): p. 6496-504. 49. Huang, S.H., Investigate the mechanism of action of a Novel Anti-Staphylococal Agent, SC-5005. 2016. 50. J B Cornett, G.D.S., Cellular lysis of Streptococcus faecalis Induced with Triton X-100. J Bacteriol., 1978 Jul. 135(1): p. 153–60. 51. Cotroneo, N., et al., Daptomycin exerts bactericidal activity without lysis of Staphylococcus aureus. Antimicrob Agents Chemother, 2008. 52(6): p. 2223-5. 52. Silverman, J.A., N.G. Perlmutter, and H.M. Shapiro, Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother, 2003. 47(8): p. 2538-44. 53. Hurdle, J.G., et al., Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat Rev Microbiol, 2011. 9(1): p. 62-75. 54. Zavascki, A.P., et al., Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother, 2007. 60(6): p. 1206-15. 55. Joe Pogliano, N.P., and Jared A. Silverman, Daptomycin-mediated reorganization of membrane architecture causes mislocalization of essential cell division proteins. J Bacteriol. , 2012 Sep. 194(17): p. 4494-504. 56. Jiang H, X.M., Bi Q, Wang Y, Li C, Self-enhanced targeted delivery of a cell wall- and membrane-active antibiotics, daptomycin, against staphylococcal pneumonia. Acta Pharm Sin B. , 2016 Jul. 6(4): p. 319-28. 57. David J. Novo, N.G.P., Richard H. Hunt, and Howard M. Shapiro, Multiparameter flow cytometric analysis of antibiotic effects on membrane potential, membrane permeability, and bacterial counts of Staphylococcus aureus and Micrococcus luteus. Antimicrob Agents Chemother. , 2000 Apr. 44(4): p. 827-34. 58. Woronowicz K, O.O., Sha D, Kay JM, Niederman RA., Effects of the protonophore carbonyl-cyanide m-chlorophenylhydrazone on intracytoplasmic membrane assembly in Rhodobacter sphaeroides. Biochim Biophys Acta. , 2015 Oct. 1847(10): p. 1119-28. 59. Fauvart M, D.G.V., Michiels J., Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J Med Microbiol. , 2011 Jun. 60(6): p. 699-709. 60. Lechner S, L.K., Bertram R., Staphylococcus aureus persisters tolerant to bactericidal antibiotics. J Mol Microbiol Biotechnol., 2012. 22(4): p. 235-44. 61. Keren I, K.N., Spoering A, Wang Y, Lewis K., Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett., 2004 Jan 230(1): p. 13-8. 62. Conlon BP, N.E., Fleck LE, LaFleur MD, Isabella VM, Coleman K, Leonard SN, Smith RD, Adkins JN, Lewis K., Activated ClpP kills persisters and eradicates a chronic biofilm infection. Nature. 21;. 2013 Nov 503(7476): p. 365-70. 63. HS., B., Pro-oxidant and anti-oxidant mechanism(s) of BHT and beta-carotene in photocarcinogenesis. Front Biosci., 2002. 7: p. 1044-55. 64. Jared A. Silverman, N.G.P., and Howard M. Shapiro, Correlation of daptomycin bactericidal activity and membrane depolarization in Staphylococcus aureus. Antimicrob Agents Chemother., 2003 Aug. 47(8): p. 2538–44. 65. Taylor SD, P.M., The action mechanism of daptomycin. Bioorg Med Chem., 2016 Dec 24(24): p. 6253-68. 66. Kuan Shion Ong, Y.L.C., and Sui Mae Lee, The role of reactive oxygen species in the antimicrobial activity of pyochelin. J Adv Res. , 2017 Jul. 8(4): p. 393-8. 67. Hayyan M, H.M., AlNashef IM, Superoxide Ion: Generation and chemical implications. Chem Rev. , 2016 Mar. 116(5): p. 3029-85. 68. Fatma Vatansever, W.C.M.A.d.M., Pinar Avci, Daniela Vecchio, Magesh Sadasivam, Asheesh Gupta, Rakkiyappan Chandran, Mahdi Karimi, Nivaldo A Parizotto, Rui Yin, George P Tegos, and Michael R Hamblin, Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond. FEMS Microbiol Rev., 2013 Nov. 37(6): p. 955-89. 69. Alugoju Phaniendra, D.B.J., and Latha Periyasamy, Free radicals: Properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem., 2015 Jan. 30(1): p. 11–26. 70. Lawrence R. Mulcahy, J.L.B., Stephen Lory, and Kim Lewis, Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J Bacteriol. , 2010 Dec 192(23): p. 6191-9. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77648 | - |
| dc.description.abstract | 細菌的抗藥性演化已造成全球公共衛生上巨大的挑戰。根據統計，抗甲氧苯青黴素之金黃色葡萄球菌的感染每年約造成11,300的美國人死亡。此外，此細菌也是人類皮膚感染的主要致病菌。由於此細菌具有對抗多數抗生素之能力，導致治療上非常棘手，因此發展新穎的抗葡萄球菌藥物是迫切需要的。我們過去的研究中證明一個小分子藥物SC5005對革蘭氏陽性菌展現良好抗菌能力，且會影響細菌細胞膜的完整性。在這裡我們進一步發現低濃度SC5005會增加細菌細胞膜的通透性，且在抑菌濃度會明顯造成細胞膜去極化的現象，進而導致大規模的細菌細胞膜破損。根據小鼠皮膚感染實驗的結果顯示，1 %的SC5005與臨床用藥的效果一樣好，都可有效降低皮膚組織內的細菌數量。
另外，先前的研究發現SC5005在有特定天然物(NP7)的存在下， 其殺菌力可加強達8,000倍以上。故我們也進一步去探討SC5005及特定天然物之間對於金黃色葡萄球菌的協同殺菌的效果以及其協同作用機制。Time- Kill Assay結果顯示，SC5005與NP7的合併可以在極短的時間內便殺死試管中所有的MRSA和懸浮狀態的休眠細菌。然而，NP7並不會加強SC5005對於人類上皮細胞的毒性，證明此NP7有很高的特異性去加強SC5005的抗菌能力。後續實驗也顯示，細菌經過SC5005的作用後可增加對於NP7的感受性，且這個藥物組合的協同抗菌能力也會隨著抗氧化劑濃度的提高而受到抑制。這表示NP7在與SC5005合併殺菌的機制上很有可能扮演氧化劑的角色。另外， NP7和SC5005的合併也會對金黃色葡萄球菌的細胞膜去極化有協同性的增強效果。以上結果顯示該組合在對MRSA的協同殺菌作用中具有多模式的作用機制。 上述實驗結果指出，SC5005可以有效降低生物體內細菌數目，且與NP7有高度協同殺菌的能力。若多加以研究及探討，這個藥物組合很有潛力成為臨床上抗甲氧苯青黴素之金黃色葡萄球菌和革蘭氏陽性細菌的皮膚感染的新藥。 | zh_TW |
| dc.description.abstract | The emergence of antibiotic resistance has imposed a serious challenge to public health worldwide. In the United States, methicillin-resistant Staphylococcus aureus (MRSA) infections claim nearly 11,300 lives each year. Besides, MRSA also is the leading cause of skin infections in the United States. As conventional antibiotics are not able to treat MRSA infections, a new antibiotic with a novel action mechanism is highly needed. Previously, our team identified a small-molecule compound, SC5005, exhibiting potent activity against Gram-positives, including clinical isolated MRSAs. At present study, we aimed to further investigate SC5005’s mode of action. Our results indicated that SC5005 at low concentration can specifically increase permeability of S. aureus membrane followed by causing membrane depolarization at 1 × MIC, leading to a complete membrane disruption at higher concentration. Furthermore, topical treatment of 1 % SC5005 was as effective as commercial antibiotic in eradicating MRSAs in skin infection mouse model.
Previously, in looking for a vehicle for SC5005’s delivery, we unexpectedly identified a nature product (NP7), which dramatically potentiated SC5005’s antibacterial activity for more than 8,000 ×. Here, we further uncovered the synergistic bactericidal mechanism of this combination and assessed their efficacy in treating MRSA skin infection. In the Time-Kill assays, this combination displayed a fast-killing activity against MRSA and planktonic persister cells as demonstrated by a complete eradication of bacteria within 3 minutes and 2 hours, respectively. In addition, NP7 had no effect on SC5005’s cytotoxicity toward human epithelial cells, indicating its synergistic effect is specific for SC5005’s antibacterial activity. Subsequent results showed that short exposure of SC5005 increased MRSA susceptibility to NP7, and the synergistic effect of this combination can be reduced by antioxidants in a dose-dependent manner, indicating NP7’s pro-oxidant activity played a crucial role in the synergistic bactericidal effect with SC5005. Also, NP7 can synergistically enhanced depolarization of S. aureus’ membrane in combined with SC5005. Above findings indicated that this combination displayed multimodal mechanism of action in the synergistic bactericidal effect against MRSA. Overall, SC5005 exhibited a non-inferior efficacy to commercial antibiotic ointment in skin-infection mouse model. As NP7 and SC5005 showed a highly synergistic effect on killing bacteria, this combination could be further developed as a topical medication for skin infections of MRSA and other Gram-positives. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T22:13:36Z (GMT). No. of bitstreams: 1 ntu-107-R05424012-1.pdf: 5151402 bytes, checksum: 38b84a924801251bd36bae9736df836c (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | Contents
致謝 i 中文摘要 ii Abstract iv Contents vi 1. Introduction 1 1.1 Staphylococcus aureus, a common human pathogen 2 1.2 Methicillin-resistant Staphylococcus aureus (MRSA) is spreading globally 3 1.3 Difficult-to-treat infections caused by MRSA 5 1.4 Alternative strategies to develop novel antibacterial agents 6 1.5 A small-molecule compound “SC5005” 7 1.6 Synergy between SC5005 and a natural product (NP7) 7 1.7 Specific aims 8 2. Materials and Methods 9 2.1 Bacterial strains and culture conditions 10 2.2 Cell line and culture condition 10 2.3 Chemicals and reagents 11 2.4 Anti-bacterial assay 12 2.5 Anti-proliferative assay 13 2.6 Checkerboard assay 14 2.7 Time-Kill Assay 15 2.8 Persistence assay 15 2.9 Biofilm eradication assay 17 2.10 C.F.U assay of SC5005 and NP7 17 2.11 Calcein leakage assay 18 2.12 Fluorescence microscopy assay 20 2.13 Propidium iodine quantification assay 21 2.14 Membrane potential assay 22 2.15 In vivo MRSA skin infection 23 2.16 Selection antibiotic-resistant MRSA USA300 25 2.17 Statistical analysis 25 3. Results 27 3.1 SC5005 specifically attacks on S. aureus membrane 28 3.2 SC5005 directly interacted with liposomes composed with phospholipids same as that of S. aureus 30 3.3 SC5005 at 1 × MIC caused membrane depolarization on S. aureus 31 3.4 SC5005 reduces MRSA load in mice skin infection model 33 3.5 Fast bactericidal activity of the combination of SC5005 and NP7 35 3.6 Cytotoxicity of the combination towards different human epithelial cell lines 36 3.7 SC5005 increased MRSA susceptibility to NP7 37 3.8 SC5005 and NP7 directly interacted with phospholipid bilayer of S. aureus model 38 3.9 The combination also showed synergistic effect on membrane depolarization 40 3.10 NP7’s pro-oxidant activity plays an important role 41 4. Discussion 44 4.1 Experimental design of NP7’ and antioxidant’ concentration 45 4.2 SC5005 exhibited higher antibacterial activity in acidic conditions 45 4.3 SC5005 was effectively against daptomycin-resistant S. aureus 46 4.4 SC5005 might directly interacts with NP7 47 4.5 Fast bactericidal activity of the combination via oxidative damaged on bacteria 48 4.6 BHT was added as a stabilizer of the combination 49 4.7 Conclusion and future prospects 49 5. Reference 51 6. Tables 64 Table 1. Anti-proliferative activity of NP7 towards different human epithelial cell lines. 65 Table 2. Anti-proliferative activity of SC5005 combined with NP7 toward different human epithelial cell lines. 66 Table 3. CDI values of the combination in calcein leakage assay, PI quantitation assay and membrane potential assay. 67 7. Figures 68 Figure 1. Membrane integrity of S. aureus after SC5005 treatment. 70 Figure 2. Percentages of membrane-compromised cells after SC5005 treatment. 71 Figure 3. Effect of SC5005 and NP7 on artificial liposomes mimicking S. aureus’ membrane. 73 Figure 4. Membrane potential measurements in S. aureus with serial SC5005 titration. 74 Figure 5. The model for mode of action of SC5005 against S. aureus. 75 Figure 6. SC5005 is effective in MRSA 33592 mice skin infection model. 76 Figure 7. SC5005 is effective in MRSA USA300 mice skin infection model. 78 Figure 8. Killing kinetic of SC5005 combined with NP7 on MRSA USA300 in broth. 80 Figure 9. The killing kinetics of SC5005 and conventional antibiotics at 10 × MIC on persister cells of MSSA 8325. 81 Figure 10. SC5005 increased MRSA susceptibility to NP7. 82 Figure 11. Percentages of PI-positive cells after treatment of the combination. 84 Figure 12. The synergistic antibacterial activity of SC5005 and NP7 can be inhibited by a variety of antioxidants. 85 Figure 13. The model of synergistic bactericidal effect between SC5005 and NP7. 86 8. Supplementary 87 Table S1. The effect of alkaline and acid on antibacterial activity of SC5005 against MRSA USA300. 88 Table S2. The antibacterial activity of SC5005 and daptomycin against S. aureus NCTC 8325 and daptomycin-resistant S. aureus. 88 Table S3. The antibacterial activity of SC5005 and mupirocin against MRSA USA300 and mupirocin-resistant MRSA USA300. 89 Table S4. The antibacterial activity of SC5005 and fusidic acid against MRSA USA300 and fusidic acid-resistant MRSA USA300. 89 Figure S1. Comparison of the progress of SSTI infection between PVL-positive and PVL-negative MRSAs. 90 Figure S2. Flow cytometric analysis of PI+ cells of S. aureus. 92 Figure S3. Flow cytometric analysis of PI+ cells of K562 human lymphoblasts. 93 Figure S4. Flow cytometric analysis of the membrane potential of drug-treated S. aureus. 95 Figure S5. Antioxidants inhibit combinatory effect of SC5005 with other nature products. 96 Figure S6. Acid-treated SC5005 was more effective than untreated SC5005 in MRSA USA300 mice skin infection model. 97 Figure S7. Other membrane active compounds showed indifferent effect with NP7. 99 Figure S8. SC5005 exhibited indifferent effect with other pro-oxidants. 100 Figure S9. Protective effect of BHT on the NP7 101 Figure S10. Selection of mupirocin- and fusidic acid-resistant MRSA USA300 103 9. List of abbreviations 104 | - |
| dc.language.iso | en | - |
| dc.subject | 膜穿孔 | zh_TW |
| dc.subject | 皮膚感染 | zh_TW |
| dc.subject | 氧化反應 | zh_TW |
| dc.subject | 膜去極化 | zh_TW |
| dc.subject | Membrane destruction | en |
| dc.subject | Membrane depolarization | en |
| dc.subject | Pro-oxidant | en |
| dc.subject | Skin-infection | en |
| dc.title | 新型細菌細胞膜標靶藥物SC5005與特定天然產物對抗甲氧苯青黴素金黄色葡萄球菌展現協同殺菌效果 | zh_TW |
| dc.title | A New Membrane Targeting Compound, SC5005, Shows Synergistic Bactericidal Activity with Certain Natural Products Against Methicillin-Resistant Staphylococcus aureus | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 史有伶;蕭崇瑋 | zh_TW |
| dc.contributor.oralexamcommittee | Yu-Ling Shih;Chung-Wai Shiau | en |
| dc.subject.keyword | 膜去極化,膜穿孔,氧化反應,皮膚感染, | zh_TW |
| dc.subject.keyword | Membrane depolarization,Membrane destruction,Pro-oxidant,Skin-infection, | en |
| dc.relation.page | 107 | - |
| dc.identifier.doi | 10.6342/NTU201800969 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2018-06-21 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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