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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳志毅(Jyh-Yih Chen) | |
| dc.contributor.author | Chih-Cheng Cheng | en |
| dc.contributor.author | 鄭志成 | zh_TW |
| dc.date.accessioned | 2022-11-23T09:02:30Z | - |
| dc.date.available | 2021-11-03 | |
| dc.date.available | 2022-11-23T09:02:30Z | - |
| dc.date.copyright | 2021-11-03 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-22 | |
| dc.identifier.citation | Reference 1. Yang, Zhanyi, et al. Rational design of short peptide variants by using Kunitzin-RE, an amphibian-derived bioactivity peptide, for acquired potent broad-spectrum antimicrobial and improved therapeutic potential of commensalism coinfection of pathogens. Journal of medicinal chemistry 62(9), 4586-4605 (2019). 2. de Breij, Anna, et al. The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms. Science translational medicine 10(423), eaan4044 (2018). 3. Zhong, Chao, et al. New Antimicrobial Peptides with Repeating Unit against Multidrug-Resistant Bacteria. ACS Infectious Diseases 7(6)1619-1637 (2021). 4. Elmahdi, S., DaSilva, L. V., Parveen, S. Antibiotic resistance of Vibrio parahaemolyticus and Vibrio vulnificus in various countries: a review. Food microbiology 57, 128-134 (2016). 5. Heng, Sing Peng, et al. Vibrio vulnificus: an environmental and clinical burden. Frontiers in microbiology 8, 997 (2017). 6. 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Antibacterial agents in clinical development : an analysis of the antibacterial clinical development pipeline, including tuberculosis. World Health Organization, Geneva, Switzerland (2017). 41. Soto, Sara M. Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm. Virulence 4(3), 223-229 (2013). 42. Campagna, S., Saint, N., Molle, G., Aumelas, A. Structure and mechanism of action of the antimicrobial peptide piscidin. Biochemistry 46(7), 1771-1778 (2007). 43. Bae, Jin Sol, et al. Piscidin: antimicrobial peptide of rock bream, Oplegnathus fasciatus. Fish shellfish immunology 51, 136-142 (2016). 44. Noga, Edward J, et al. Piscidin 4, a novel member of the piscidin family of antimicrobial peptides. Comparative Biochemistry Physiology Part B: Biochemistry Molecular Biology 152(4), 299-305 (2009). 45. Fernandes, J. M., Ruangsri, J., Kiron, V. Atlantic cod piscidin and its diversification through positive selection. Plos one 5(3), e9501 (2010). 46. Papo, N., Oren, Z., Pag, U., Sahl, H. G., Shai, Y. The consequence of sequence alteration of an amphipathic α-helical antimicrobial peptide and its diastereomers. Journal of Biological Chemistry 277(37), 33913-33921 (2002). 47. Sancho-Vaello, Enea, et al. Structural remodeling and oligomerization of human cathelicidin on membranes suggest fibril-like structures as active species. Scientific reports 7(1), 15371 (2017). 48. Brown, K. L., Hancock, R. E. Cationic host defense (antimicrobial) peptides. Current opinion in immunology 18(1), 24-30 (2006). 49. Kim, Lewis. Persister cells. Annual review of microbiology 64, 357-372 (2010). 50. Lee, M. T., Dinh, A., Nguyen, S., Krucke, G., Tran, T. Late-onset Vibrio vulnificus septicemia without cirrhosis. Proc (Bayl Univ Med Cent) 32(2), 286-288 (2019). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79516 | - |
| dc.description.abstract | "由於多重抗藥性 (Multidrug resistant, MDR) 細菌感染的案件層出不窮，發展新型態的抗生素已成為當務之急。抗菌胜肽 (Antimicrobial peptides, AMPs) 是一群獨特的小分子，在抵禦病原菌入侵及先天性免疫中扮演著重要的角色。近年來，已有研究證實遍布於各種生物之間不同種類的抗菌胜肽，例如 piscidin、defensin、cathelecidin 及 cecropin等。這些分子擁有強大的抗微生物、抗腫瘤以及抗發炎的能力，使其有機會在臨床治療上發光發熱。然而，抗菌胜肽因為藥物動力學，以及在活體具有顯著的細胞毒性，因此在臨床發展上受到重重的限制。因此，我們著手進行新型抗菌胜肽的開發，改善 Tilapia piscidin 1 (TP1) 及 Tilapia piscidin (TP2) 的治療特性。在本次研究中，我們利用一對低活性的 Tilapia piscidin 衍生物，TP1 及 TP2 作為模板，並且按照我們的理念，替換序列中選定的胺基酸來恢復兩親性平衡以及正電荷。藉此我們開發出兩個高活性且低毒性的抗菌胜肽，分別為 TP1-1 及 TP2-5 。在不同的溫度、pH值、蛋白酶以及人類血清的環境中，仍保有良好的活性，且在小鼠的表皮上幾乎沒有毒性。在創傷弧菌 (Vibrio vulnificus) 感染小鼠皮膚傷口的模式中，TP1-1 (6.25 微克/老鼠) 與 doxycycline (0.048微克/老鼠) 的治療結果相似，分別救活了 20% 及 25% 的小鼠，然而 TP2-5 (12.5微克/老鼠) 的存活率則高達 80% 。總而言之，透過以上的胜肽設計策略，我們發展出在活體中具有顯著活性的抗菌胜肽。因此，本研究構想可應用於新型抗菌胜肽的開發，讓未來的臨床試驗及臨床應用所遇到的瓶頸增添一線生機。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T09:02:30Z (GMT). No. of bitstreams: 1 U0001-2909202109442200.pdf: 8575981 bytes, checksum: 6f3e00b2f9c8215af59cd8ec01437a53 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "Table of Contents 謝辭 I 中文摘要 II Abstract III Table of contents V 1. Introduction 1 1.1 Antibiotic resistance 1 1.2 Vibrio vulnificus 1 1.3 First-line treatment and other antibiotics 2 1.4 Antimicrobial peptide 3 1.5 Tilapia piscidin 3 1.6 The concept of antimicrobial peptide designs 4 1.7 Perspective and hypothesis 5 2. Materials and methods 6 2.1 Key resources table 6 2.2 Animals 10 2.2.1 Mice 10 2.2.2 Fish 10 2.3 Bacteria culture conditions 10 2.4 Bacterial inoculum and quantification 11 2.5 Cell culture conditions 11 2.6 CD analysis 11 2.7 Antimicrobial assay 12 2.8 Hemolysis assay 13 2.9 Time-kill kinetics 13 2.10 Resistance development 14 2.11 Effects of pH, temperature, and proteases on peptide activity 14 2.12 Human serum stability testing 14 2.13 Checkerboard assay 15 2.14 LPS neutralization assay 16 2.15 NPN 17 2.16 DiBAC 17 2.17 SEM and TEM sample preparation 18 2.18 Antibiofilm assay 18 2.19 Cell viability 19 2.20 In vivo acute dermal toxicity analysis 21 2.21 In vivo murine skin wound infection model 21 2.22 Statistics 23 3. Results 24 3.1 Design of TP1-1 and TP2-5 24 3.2 Circular dichroism spectroscopy of TP1-1 and TP2-5 25 3.3 Antimicrobial activity 25 3.4 Hemolytic analysis 26 3.5 Time killing kinetic 27 3.6 Resistance development 27 3.7 Effects of pH, temperature, proteolytic enzymes, and human serum on antimicrobial activity 28 3.8 Checkerboard assay 29 3.9 Mechanism of action 30 3.10 Morphological observation of bacteria 31 3.11 Biofilm inhibition and eradication 32 3.12 Cell viability 33 3.13 Acute dermal toxicity 34 3.14 In vivo antimicrobial activity 35 4. Discussion 36 5. Conclusion 41 6. Reference 43 7. Tables and Figures 50 8. Supplementary data 83" | |
| dc.language.iso | en | |
| dc.title | 透過設計與特性分析新型羅非魚抗菌胜肽 TP1-1 及 TP2-5 用於提升創傷弧菌感染小鼠皮膚傷口之抗菌活性及治療效果 | zh_TW |
| dc.title | Design and Characterization of Novel Tilapia Piscidin TP1-1 and TP2-5 to Improve Antimicrobial Activity and Therapeutic Efficiency against Murine Skin Wound Infection Induced by Vibrio vulnificus | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李宗徽(Hsin-Tsai Liu),潘婕玉(Chih-Yang Tseng),韓玉山,陳威戎 | |
| dc.subject.keyword | 抗菌胜肽,吳郭魚抗菌胜肽,多重抗藥性細菌,創傷弧菌,小鼠皮膚傷口感染模式, | zh_TW |
| dc.subject.keyword | Antimicrobial peptides (AMPs),tilapia piscidins (TPs),multidrug resistant (MDR) bacteria,Vibrio vulnificus,murine wound infection model, | en |
| dc.relation.page | 102 | |
| dc.identifier.doi | 10.6342/NTU202103448 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-10-24 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 漁業科學研究所 | zh_TW |
| 顯示於系所單位： | 漁業科學研究所 | |
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