利用大腸桿菌蛋白體微陣列晶片系統性探討抗菌肽的胞內作用目標

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：12

、訪客IP：3.145.91.152

姓名

何宇軒(Yu-Hsuan Ho) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

利用大腸桿菌蛋白體微陣列晶片系統性探討抗菌肽的胞內作用目標
(Systematic Analysis of Intracellular Targeting Antimicrobial Peptides Using E. coli Proteome Microarray)

相關論文

★ 以生物資訊分析與實驗驗證探討大腸桿菌蛋白質體晶片找出的乳鐵胜肽B胞內目標蛋白	★ 結合奈米脂粒與抗體微陣列晶片的高通量快速檢測系統之發展並應用於婦女子宮頸炎病因之診斷與研究
★ 蛋白質 G 與具硫基反應性的釕複合物之生物接合作為螢光免疫試驗的通用試劑	★ 利用微陣列蛋白質晶片帥選GNRA tetraloop結合蛋白
★ 利用大腸桿菌蛋白質體晶片分析新生兒血液中的免疫球蛋白	★ 利用大腸桿菌蛋白質體晶片找出參與第一型線毛表現之細菌蛋白質
★ 利用人類蛋白質體微陣列晶片探究C型肝炎病毒非轉譯區與宿主之交互作用	★ 利用大腸桿菌蛋白質體晶片找出與2-氧基組胺酸交互作用之蛋白質
★ 發展微珠式96孔過濾盤競爭型免疫分析法偵測硫酸紫菌素	★ 異質性核醣核酸蛋白K (hnRNP K) 抑制成熟miRNA-122轉錄後調控機制之研究
★ 利用酵母菌蛋白質體晶片找出與前信使核糖核酸加工因子19泛素連接?經泛素化作用之受質	★ 腸道共生黴菌與酒精性肝病的相關性
★ 在大腸桿菌與酵母菌蛋白質體晶片中量化其蛋白質的濃度	★ 應用大腸桿菌與酵母菌蛋白質體晶片系統性分析抗菌肽及抗生素作用之目標蛋白質

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

[檢視]

[下載]

本電子論文使用權限為同意立即開放。
已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中)

抗藥性在近年來已受到越來越多的關注，因為缺乏新穎的抗生素，一些平常的感染在未來或許都會對人類造成致命的威脅。因此，對新型抗生素的需求是極為迫切的。天然的抗菌肽是一種演化上非常重要的防禦系統，他們保護了多細胞生物免於微生物的侵襲。目前比較為人所知的抗菌肽抗菌機制主要是透過破壞微生物細胞膜的完整性以達到殺死微生物的目的，然而，有一部分的抗菌肽已被證實會穿過微生物的細胞膜，並且進一步影響微生物的胞內生理作用。而這些有胞內作用的抗菌肽一旦進入細胞內就會影響不只一個細菌蛋白質的作用，因此，他們可能有非常複雜的胞內抗菌機制。而這項複雜的特性也使得這群抗菌肽成為一個新的發展新型抗生素的來源，因為對細菌來說，要對這樣複雜的機制產生抗藥性也是相對的比較困難。目前，已經有一些具有胞內活性的抗菌肽已經被辨識出來，但是他們的胞內作用機制仍然是未知的，像是Bac 7, Lactoferricin B (Lfcin B), P-Der及PR-39。
為了瞭解這些抗菌肽的胞內作用機制，我們先使用大腸桿菌蛋白體晶片去找出Lfcin B可能的作用目標蛋白。晶片結果顯示，Lfcin B對於兩個蛋白質有很強的親和力(basR and creB)，而這兩個蛋白質皆是屬於雙因子調控系統的反應子(response regulator of two component system)。為了進一步的分析，我們使用了一些實驗及生物資訊的分析去釐清Lfcin B與這兩個蛋白質間的關係。蛋白質凝膠電泳與激酶實驗顯示Lfcin B影響了這兩個蛋白質的磷酸化能力。抗菌實驗顯示Lfcin B減低了大腸桿菌對特定環境的反應能力，像是在充滿鐵離子與微酸的環境以及探來源受到限制的環境下。
為了更系統性的分析有胞內活性的抗菌肽，我們也針對Bac 7, P-Der 及PR-39與晶片進行反應，同時，也加入之前已分析過的Lfcin B的晶片資料。首先，我們先分析各個抗菌肽獨特的蛋白質目標，此結果顯示。Bac 7主要影響DNA的合成藉由攻擊purine代謝的功能。Lfcin B主要攻擊轉錄以及碳水化合物代謝的相關的功能。P-Der 主要影響細胞內的小分子代謝作用。PR-39攻擊許多跟RNA相關的細胞功能及合成。此外，細胞途徑的分析也發現Bac 7 及Lfcin B共同攻擊purine的代謝路徑，Lfcin B及 PR-39共同攻擊細胞內的脂多糖的合成路徑。更進一步，我們分析了四個抗菌肽共同的目標蛋白，發現他們共同的作用目標為精氨酸脫梭酵素，因此，我們用抗菌實驗進一步去驗證，發現這四種抗菌肽的確都有非常好的抑菌效果當細菌需要使用精氨酸脫梭酵素來當作存活的手段時。我們的發現使得對於這些胞內作用的抗菌肽有了更多更深入的了解，也提供了後續多研究的方向。

摘要(英)

It is a wide acceptance that antibiotics resistance now has become a global issue among the world. According to a recent report conducted by World Health Organization (WHO), the multidrug-resistant tuberculosis alone causes more than 150,000 deaths each year. Because of the lack of conventional antibiotics, normal infections could also become lethal. It’s an urgent need to develop novel strategies against the antibiotics resistance strains. The natural antimicrobial peptide (AMP) is an evolutionary important defense system for multicellular organisms to protect them from the invasions of the microbes. Although the well-known mechanism for AMP to kill the microbes is via the membrane permeabilization, some AMPs still have the ability to interrupt the intracellular cellular functions of microbes. The intracellular targeting AMPs may influence more than one protein inside the cells; thus, the intracellular targeting AMPs have multiple modes of actions to inhibit the microbes. The complex mechanisms of intracellular targeting AMPs makes them become attractive resource for developing novel strategies against microbes because for microorganisms, it’s hard for them to exhibit the antimicrobial resistance to such complicated process. Yet several intracellular targeting AMPs have been identified, some of them still have the unknown target and function such as Bactenecin 7, Lactoferricin B, a hybrid of Pleurocidin and Dermaseptin (P-Der) and a proline-arginine-rich antibacterial peptide (PR-39). In addition, there is no systematic analysis to study the mechanisms of intracellular targeting AMPs.
To elucidate the intracellular behavior of Lactoferricin B (Lfcin B), we first used E. coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system (TCS). For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli’s tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of TCS directly.
To identify the protein targets of 3 intracellular active antimicrobial peptides, Bac 7, P-Der and PR-39, we used the E. coli proteome microarray to identify the hits for each AMP. In addition, to provide systematic level analysis, we also included the data of Lactoferricin B (Lfcin B) from our previous studies to give a more comprehensive analysis of 4 intracellular targeting antimicrobial peptides using several bioinformatics methods. First, we analyzed the unique protein hits of each AMP. Our results indicate that Bac 7 mainly target in the DNA synthesis via influencing the purine metabolism. Lfcin B mainly attacks the transcriptional and cellular carbohydrate metabolism related functions. P-Der affects several catabolic processes of small molecules. PR-39 shows strong preference to recognize the proteins that involved in RNA related cellular processes. In addition, the KEGG analysis of unique hits of each AMP indicates that the synergistic effects may appear among these 4 peptides. Bac 7 and Lfcin B may target on the same pathway, purine metabolism; while, Lfcin B and PR-39 both target on Lipopolysaccharide biosynthesis. Furthermore, we analyzed the common hits of 4 AMPs and this result indicates that these 4 AMPs all target on the arginine decarboxylase. To validate this finding, the antimicrobial assay was conducted. The 4 AMPs all leaded to a significant growth inhibition of bacteria under the extreme acidic environment (pH < 3) compared to a membrane active peptide, Cecropin P1.

關鍵字(中)

★ 蛋白質體晶片
★ 抗菌肽
★ 生物資訊

關鍵字(英)

★ proteome microarray
★ antimicrobial peptide
★ bioinformatics

論文目次

中文摘要 I
Abstract III
誌謝 V
List of figures VII
List of tables VIII
Chapter I: Literature review: mechanisms of intracellular targeting antimicrobial peptides 1
Abstract 1
Introduction 2
Comments 10
Chapter II. Lactoferricin B Inhibits the Phosphorylation of the Two-Component System Response Regulators BasR and CreB 11
Abstract 11
Introduction 11
Materials and methods 13
Results 18
Discussions 23
Chapter III. Systematic analysis of four intracellular targeting antimicrobial peptides, Bactenecin 7, Lactoferricin B, P-Der and PR-39, using E. coli proteome microarray 30
Abstract 30
Introduction 31
Materials and methods 33
Results 35
Discussions 44
References 46
Figures 58
Tables 80

參考文獻

1. Davies J, Davies D (2010) Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74: 417-433.
2. Wang J, Wong ES, Whitley JC, Li J, Stringer JM, et al. (2011) Ancient antimicrobial peptides kill antibiotic-resistant pathogens: Australian mammals provide new options. PLoS One 6: e24030.
3. Wang G, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37: D933-937.
4. Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415: 389-395.
5. Hancock RE, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24: 1551-1557.
6. Tu YH, Ho YH, Chuang YC, Chen PC, Chen CS (2011) Identification of lactoferricin B intracellular targets using an Escherichia coli proteome chip. PLoS One 6: e28197.
7. Ho YH, Sung TC, Chen CS (2012) Lactoferricin B inhibits the phosphorylation of the two-component system response regulators BasR and CreB. Mol Cell Proteomics 11: M111 014720.
8. Park SC, Park Y, Hahm KS (2011) The role of antimicrobial peptides in preventing multidrug-resistant bacterial infections and biofilm formation. Int J Mol Sci 12: 5971-5992.
9. Chan DI, Prenner EJ, Vogel HJ (2006) Tryptophan- and arginine-rich antimicrobial peptides: structures and mechanisms of action. Biochim Biophys Acta 1758: 1184-1202.
10. Sahl HG, Jack RW, Bierbaum G (1995) Biosynthesis and biological activities of lantibiotics with unique post-translational modifications. Eur J Biochem 230: 827-853.
11. Brotz H, Bierbaum G, Markus A, Molitor E, Sahl HG (1995) Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism? Antimicrob Agents Chemother 39: 714-719.
12. Molitor E, Kluczny C, Brotz H, Bierbaum G, Jack R, et al. (1996) Effects of the lantibiotic mersacidin on the morphology of staphylococci. Zentralbl Bakteriol 284: 318-328.
13. Brotz H, Bierbaum G, Leopold K, Reynolds PE, Sahl HG (1998) The lantibiotic mersacidin inhibits peptidoglycan synthesis by targeting lipid II. Antimicrob Agents Chemother 42: 154-160.
14. Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, et al. (1985) Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76: 1427-1435.
15. Lehrer RI, Barton A, Daher KA, Harwig SS, Ganz T, et al. (1989) Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest 84: 553-561.
16. de Leeuw E, Li C, Zeng P, Li C, Diepeveen-de Buin M, et al. (2010) Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II. FEBS Lett 584: 1543-1548.
17. Park CB, Kim HS, Kim SC (1998) Mechanism of action of the antimicrobial peptide buforin II: buforin II kills microorganisms by penetrating the cell membrane and inhibiting cellular functions. Biochem Biophys Res Commun 244: 253-257.
18. Yi GS, Park CB, Kim SC, Cheong C (1996) Solution structure of an antimicrobial peptide buforin II. FEBS Lett 398: 87-90.
19. Uyterhoeven ET, Butler CH, Ko D, Elmore DE (2008) Investigating the nucleic acid interactions and antimicrobial mechanism of buforin II. FEBS Lett 582: 1715-1718.
20. Yonezawa A, Kuwahara J, Fujii N, Sugiura Y (1992) Binding of tachyplesin I to DNA revealed by footprinting analysis: significant contribution of secondary structure to DNA binding and implication for biological action. Biochemistry 31: 2998-3004.
21. Masuda K, Ohta M, Ito M, Ohsuka S, Kaneda T, et al. (1994) Bactericidal action of tachyplesin I against oral streptococci. Oral Microbiol Immunol 9: 77-80.
22. Yonezawa A, Sugiura Y (1992) Tachyplesin I as a model peptide for antiparallel beta-sheet DNA binding motif. Nucleic Acids Symp Ser: 161-162.
23. Kawano K, Yoneya T, Miyata T, Yoshikawa K, Tokunaga F, et al. (1990) Antimicrobial peptide, tachyplesin I, isolated from hemocytes of the horseshoe crab (Tachypleus tridentatus). NMR determination of the beta-sheet structure. J Biol Chem 265: 15365-15367.
24. Ramamoorthy A, Thennarasu S, Tan A, Gottipati K, Sreekumar S, et al. (2006) Deletion of all cysteines in tachyplesin I abolishes hemolytic activity and retains antimicrobial activity and lipopolysaccharide selective binding. Biochemistry 45: 6529-6540.
25. Doherty T, Waring AJ, Hong M (2006) Peptide-lipid interactions of the beta-hairpin antimicrobial peptide tachyplesin and its linear derivatives from solid-state NMR. Biochim Biophys Acta 1758: 1285-1291.
26. Rao AG (1999) Conformation and antimicrobial activity of linear derivatives of tachyplesin lacking disulfide bonds. Arch Biochem Biophys 361: 127-134.
27. Imura Y, Nishida M, Ogawa Y, Takakura Y, Matsuzaki K (2007) Action mechanism of tachyplesin I and effects of PEGylation. Biochim Biophys Acta 1768: 1160-1169.
28. Hsu CH, Chen C, Jou ML, Lee AY, Lin YC, et al. (2005) Structural and DNA-binding studies on the bovine antimicrobial peptide, indolicidin: evidence for multiple conformations involved in binding to membranes and DNA. Nucleic Acids Res 33: 4053-4064.
29. Selsted ME, Novotny MJ, Morris WL, Tang YQ, Smith W, et al. (1992) Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils. J Biol Chem 267: 4292-4295.
30. van Abel RJ, Tang YQ, Rao VS, Dobbs CH, Tran D, et al. (1995) Synthesis and characterization of indolicidin, a tryptophan-rich antimicrobial peptide from bovine neutrophils. Int J Pept Protein Res 45: 401-409.
31. Subbalakshmi C, Sitaram N (1998) Mechanism of antimicrobial action of indolicidin. FEMS Microbiol Lett 160: 91-96.
32. del Castillo FJ, del Castillo I, Moreno F (2001) Construction and characterization of mutations at codon 751 of the Escherichia coli gyrB gene that confer resistance to the antimicrobial peptide microcin B17 and alter the activity of DNA gyrase. J Bacteriol 183: 2137-2140.
33. Vizan JL, Hernandez-Chico C, del Castillo I, Moreno F (1991) The peptide antibiotic microcin B17 induces double-strand cleavage of DNA mediated by E. coli DNA gyrase. EMBO J 10: 467-476.
34. Pierrat OA, Maxwell A (2005) Evidence for the role of DNA strand passage in the mechanism of action of microcin B17 on DNA gyrase. Biochemistry 44: 4204-4215.
35. Parks WM, Bottrill AR, Pierrat OA, Durrant MC, Maxwell A (2007) The action of the bacterial toxin, microcin B17, on DNA gyrase. Biochimie 89: 500-507.
36. Mukhopadhyay J, Sineva E, Knight J, Levy RM, Ebright RH (2004) Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel. Mol Cell 14: 739-751.
37. Bayro MJ, Mukhopadhyay J, Swapna GV, Huang JY, Ma LC, et al. (2003) Structure of antibacterial peptide microcin J25: a 21-residue lariat protoknot. J Am Chem Soc 125: 12382-12383.
38. Adelman K, Yuzenkova J, La Porta A, Zenkin N, Lee J, et al. (2004) Molecular mechanism of transcription inhibition by peptide antibiotic Microcin J25. Mol Cell 14: 753-762.
39. Yuzenkova J, Delgado M, Nechaev S, Savalia D, Epshtein V, et al. (2002) Mutations of bacterial RNA polymerase leading to resistance to microcin j25. J Biol Chem 277: 50867-50875.
40. Chesnokova LS, Slepenkov SV, Witt SN (2004) The insect antimicrobial peptide, L-pyrrhocoricin, binds to and stimulates the ATPase activity of both wild-type and lidless DnaK. FEBS Lett 565: 65-69.
41. Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, et al. (2001) The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry 40: 3016-3026.
42. Longhi C, Conte MP, Bellamy W, Seganti L, Valenti P (1994) Effect of lactoferricin B, a pepsin-generated peptide of bovine lactoferrin, on Escherichia coli HB101 (pRI203) entry into HeLa cells. Med Microbiol Immunol 183: 77-85.
43. Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, et al. (1997) Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice. Jpn J Cancer Res 88: 184-190.
44. Hwang PM, Zhou N, Shan X, Arrowsmith CH, Vogel HJ (1998) Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin. Biochemistry 37: 4288-4298.
45. Ulvatne H, Samuelsen O, Haukland HH, Kramer M, Vorland LH (2004) Lactoferricin B inhibits bacterial macromolecular synthesis in Escherichia coli and Bacillus subtilis. FEMS Microbiol Lett 237: 377-384.
46. Schnapp D, Kemp GD, Smith VJ (1996) Purification and characterization of a proline-rich antibacterial peptide, with sequence similarity to bactenecin-7, from the haemocytes of the shore crab, Carcinus maenas. Eur J Biochem 240: 532-539.
47. Podda E, Benincasa M, Pacor S, Micali F, Mattiuzzo M, et al. (2006) Dual mode of action of Bac7, a proline-rich antibacterial peptide. Biochim Biophys Acta 1760: 1732-1740.
48. Ghiselli R, Giacometti A, Cirioni O, Circo R, Mocchegiani F, et al. (2003) Neutralization of endotoxin in vitro and in vivo by Bac7(1-35), a proline-rich antibacterial peptide. Shock 19: 577-581.
49. Tani A, Lee S, Oishi O, Aoyagi H, Ohno M (1995) Interaction of the fragments characteristic of bactenecin 7 with phospholipid bilayers and their antimicrobial activity. J Biochem 117: 560-565.
50. Boman HG, Agerberth B, Boman A (1993) Mechanisms of action on Escherichia coli of cecropin P1 and PR-39, two antibacterial peptides from pig intestine. Infect Immun 61: 2978-2984.
51. Agerberth B, Lee JY, Bergman T, Carlquist M, Boman HG, et al. (1991) Amino acid sequence of PR-39. Isolation from pig intestine of a new member of the family of proline-arginine-rich antibacterial peptides. Eur J Biochem 202: 849-854.
52. Gudmundsson GH, Magnusson KP, Chowdhary BP, Johansson M, Andersson L, et al. (1995) Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39. Proc Natl Acad Sci U S A 92: 7085-7089.
53. Jia X, Patrzykat A, Devlin RH, Ackerman PA, Iwama GK, et al. (2000) Antimicrobial peptides protect coho salmon from Vibrio anguillarum infections. Appl Environ Microbiol 66: 1928-1932.
54. Patrzykat A, Friedrich CL, Zhang L, Mendoza V, Hancock RE (2002) Sublethal concentrations of pleurocidin-derived antimicrobial peptides inhibit macromolecular synthesis in Escherichia coli. Antimicrob Agents Chemother 46: 605-614.
55. Edgerton M, Raj PA, Levine MJ (1995) Surface-modified poly(methyl methacrylate) enhances adsorption and retains anticandidal activities of salivary histatin 5. J Biomed Mater Res 29: 1277-1286.
56. Tsai H, Bobek LA (1997) Human salivary histatin-5 exerts potent fungicidal activity against Cryptococcus neoformans. Biochim Biophys Acta 1336: 367-369.
57. Wunder D, Dong J, Baev D, Edgerton M (2004) Human salivary histatin 5 fungicidal action does not induce programmed cell death pathways in Candida albicans. Antimicrob Agents Chemother 48: 110-115.
58. Kumar R, Chadha S, Saraswat D, Bajwa JS, Li RA, et al. (2011) Histatin 5 uptake by Candida albicans utilizes polyamine transporters Dur3 and Dur31 proteins. J Biol Chem 286: 43748-43758.
59. Koshlukova SE, Lloyd TL, Araujo MW, Edgerton M (1999) Salivary histatin 5 induces non-lytic release of ATP from Candida albicans leading to cell death. J Biol Chem 274: 18872-18879.
60. Zhang L, Scott MG, Yan H, Mayer LD, Hancock RE (2000) Interaction of polyphemusin I and structural analogs with bacterial membranes, lipopolysaccharide, and lipid monolayers. Biochemistry 39: 14504-14514.
61. Masuda M, Nakashima H, Ueda T, Naba H, Ikoma R, et al. (1992) A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12,Lys7]-polyphemusin II). Biochem Biophys Res Commun 189: 845-850.
62. Powers JP, Martin MM, Goosney DL, Hancock RE (2006) The antimicrobial peptide polyphemusin localizes to the cytoplasm of Escherichia coli following treatment. Antimicrob Agents Chemother 50: 1522-1524.
63. Stensvag K, Haug T, Sperstad SV, Rekdal O, Indrevoll B, et al. (2008) Arasin 1, a proline-arginine-rich antimicrobial peptide isolated from the spider crab, Hyas araneus. Dev Comp Immunol 32: 275-285.
64. Imjongjirak C, Amparyup P, Tassanakajon A (2011) Two novel antimicrobial peptides, arasin-likeSp and GRPSp, from the mud crab Scylla paramamosain, exhibit the activity against some crustacean pathogenic bacteria. Fish Shellfish Immunol 30: 706-712.
65. Paulsen VS, Blencke HM, Benincasa M, Haug T, Eksteen JJ, et al. (2013) Structure-activity relationships of the antimicrobial peptide arasin 1 - and mode of action studies of the N-terminal, proline-rich region. PLoS One 8: e53326.
66. Yang ST, Yub Shin SY, Kim YC, Kim Y, Hahm KS, et al. (2002) Conformation-dependent antibiotic activity of tritrpticin, a cathelicidin-derived antimicrobial peptide. Biochem Biophys Res Commun 296: 1044-1050.
67. Schibli DJ, Hwang PM, Vogel HJ (1999) Structure of the antimicrobial peptide tritrpticin bound to micelles: a distinct membrane-bound peptide fold. Biochemistry 38: 16749-16755.
68. Yang ST, Shin SY, Hahm KS, Kim JI (2006) Different modes in antibiotic action of tritrpticin analogs, cathelicidin-derived Trp-rich and Pro/Arg-rich peptides. Biochim Biophys Acta 1758: 1580-1586.
69. Wang Z, Wang G (2004) APD: the Antimicrobial Peptide Database. Nucleic Acids Res 32: D590-592.
70. Yamamoto K, Hirao K, Oshima T, Aiba H, Utsumi R, et al. (2005) Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli. J Biol Chem 280: 1448-1456.
71. Gao R, Tao Y, Stock AM (2008) System-level mapping of Escherichia coli response regulator dimerization with FRET hybrids. Mol Microbiol 69: 1358-1372.
72. Hagiwara D, Yamashino T, Mizuno T (2004) A Genome-wide view of the Escherichia coli BasS-BasR two-component system implicated in iron-responses. Biosci Biotechnol Biochem 68: 1758-1767.
73. Miller SI, Kukral AM, Mekalanos JJ (1989) A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A 86: 5054-5058.
74. Bader MW, Sanowar S, Daley ME, Schneider AR, Cho U, et al. (2005) Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 122: 461-472.
75. Groisman EA (2001) The pleiotropic two-component regulatory system PhoP-PhoQ. J Bacteriol 183: 1835-1842.
76. Brodsky IE, Gunn JS (2005) A bacterial sensory system that activates resistance to innate immune defenses: potential targets for antimicrobial therapeutics. Mol Interv 5: 335-337.
77. McPhee JB, Lewenza S, Hancock RE (2003) Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol Microbiol 50: 205-217.
78. Tomita M, Wakabayashi H, Shin K, Yamauchi K, Yaeshima T, et al. (2009) Twenty-five years of research on bovine lactoferrin applications. Biochimie 91: 52-57.
79. Hoek KS, Milne JM, Grieve PA, Dionysius DA, Smith R (1997) Antibacterial activity in bovine lactoferrin-derived peptides. Antimicrob Agents Chemother 41: 54-59.
80. Dionysius DA, Grieve PA, Milne JM (1993) Forms of lactoferrin: their antibacterial effect on enterotoxigenic Escherichia coli. J Dairy Sci 76: 2597-2600.
81. Mader JS, Salsman J, Conrad DM, Hoskin DW (2005) Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Mol Cancer Ther 4: 612-624.
82. Mader JS, Smyth D, Marshall J, Hoskin DW (2006) Bovine lactoferricin inhibits basic fibroblast growth factor- and vascular endothelial growth factor165-induced angiogenesis by competing for heparin-like binding sites on endothelial cells. Am J Pathol 169: 1753-1766.
83. Ulvatne H, Haukland HH, Olsvik O, Vorland LH (2001) Lactoferricin B causes depolarization of the cytoplasmic membrane of Escherichia coli ATCC 25922 and fusion of negatively charged liposomes. FEBS Lett 492: 62-65.
84. Haukland HH, Ulvatne H, Sandvik K, Vorland LH (2001) The antimicrobial peptides lactoferricin B and magainin 2 cross over the bacterial cytoplasmic membrane and reside in the cytoplasm. FEBS Lett 508: 389-393.
85. Chen CS, Sullivan S, Anderson T, Tan AC, Alex PJ, et al. (2009) Identification of novel serological biomarkers for inflammatory bowel disease using Escherichia coli proteome chip. Mol Cell Proteomics 8: 1765-1776.
86. Chen CS, Korobkova E, Chen H, Zhu J, Jian X, et al. (2008) A proteome chip approach reveals new DNA damage recognition activities in Escherichia coli. Nat Methods 5: 69-74.
87. Kitagawa M, Ara T, Arifuzzaman M, Ioka-Nakamichi T, Inamoto E, et al. (2005) Complete set of ORF clones of Escherichia coli ASKA library (a complete set of E. coli K-12 ORF archive): unique resources for biological research. DNA Res 12: 291-299.
88. Zhu X, Gerstein M, Snyder M (2006) ProCAT: a data analysis approach for protein microarrays. Genome Biol 7: R110.
89. Froelich JM, Tran K, Wall D (2006) A pmrA constitutive mutant sensitizes Escherichia coli to deoxycholic acid. J Bacteriol 188: 1180-1183.
90. Avison MB, Horton RE, Walsh TR, Bennett PM (2001) Escherichia coli CreBC is a global regulator of gene expression that responds to growth in minimal media. J Biol Chem 276: 26955-26961.
91. Murray J, Marusich MF, Capaldi RA, Aggeler R (2004) Focused proteomics: monoclonal antibody-based isolation of the oxidative phosphorylation machinery and detection of phosphoproteins using a fluorescent phosphoprotein gel stain. Electrophoresis 25: 2520-2525.
92. Schulenberg B, Goodman TN, Aggeler R, Capaldi RA, Patton WF (2004) Characterization of dynamic and steady-state protein phosphorylation using a fluorescent phosphoprotein gel stain and mass spectrometry. Electrophoresis 25: 2526-2532.
93. Schulenberg B, Aggeler R, Beechem JM, Capaldi RA, Patton WF (2003) Analysis of steady-state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J Biol Chem 278: 27251-27255.
94. Steinberg TH, Agnew BJ, Gee KR, Leung WY, Goodman T, et al. (2003) Global quantitative phosphoprotein analysis using Multiplexed Proteomics technology. Proteomics 3: 1128-1144.
95. Hayduk EJ, Choe LH, Lee KH (2004) A two-dimensional electrophoresis map of Chinese hamster ovary cell proteins based on fluorescence staining. Electrophoresis 25: 2545-2556.
96. Ge Y, Rajkumar L, Guzman RC, Nandi S, Patton WF, et al. (2004) Multiplexed fluorescence detection of phosphorylation, glycosylation, and total protein in the proteomic analysis of breast cancer refractoriness. Proteomics 4: 3464-3467.
97. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, et al. (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37: W202-208.
98. Gaulton A, Attwood TK (2003) Motif3D: Relating protein sequence motifs to 3D structure. Nucleic Acids Res 31: 3333-3336.
99. Itou H, Tanaka I (2001) The OmpR-family of proteins: insight into the tertiary structure and functions of two-component regulator proteins. J Biochem 129: 343-350.
100. Shin D, Groisman EA (2005) Signal-dependent binding of the response regulators PhoP and PmrA to their target promoters in vivo. J Biol Chem 280: 4089-4094.
101. Hoch JA (2000) Two-component and phosphorelay signal transduction. Curr Opin Microbiol 3: 165-170.
102. Nikel PI, Zhu J, San KY, Mendez BS, Bennett GN (2009) Metabolic flux analysis of Escherichia coli creB and arcA mutants reveals shared control of carbon catabolism under microaerobic growth conditions. J Bacteriol 191: 5538-5548.
103. Lehrer RI, Ganz T (1999) Antimicrobial peptides in mammalian and insect host defence. Curr Opin Immunol 11: 23-27.
104. Cariss SJ, Tayler AE, Avison MB (2008) Defining the growth conditions and promoter-proximal DNA sequences required for activation of gene expression by CreBC in Escherichia coli. J Bacteriol 190: 3930-3939.
105. Makino K, Amemura M, Kawamoto T, Kimura S, Shinagawa H, et al. (1996) DNA binding of PhoB and its interaction with RNA polymerase. J Mol Biol 259: 15-26.
106. Quigley EM, Quera R (2006) Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology 130: S78-90.
107. Takeuchi K, Bjarnason I, Laftah AH, Latunde-Dada GO, Simpson RJ, et al. (2005) Expression of iron absorption genes in mouse large intestine. Scand J Gastroenterol 40: 169-177.
108. Simpson RJ, Peters TJ (1990) Forms of soluble iron in mouse stomach and duodenal lumen: significance for mucosal uptake. Br J Nutr 63: 79-89.
109. Chamnongpol S, Dodson W, Cromie MJ, Harris ZL, Groisman EA (2002) Fe(III)-mediated cellular toxicity. Mol Microbiol 45: 711-719.
110. Leitch GJ, Ceballos C (2009) A role for antimicrobial peptides in intestinal microsporidiosis. Parasitology 136: 175-181.
111. Fabich AJ, Jones SA, Chowdhury FZ, Cernosek A, Anderson A, et al. (2008) Comparison of carbon nutrition for pathogenic and commensal Escherichia coli strains in the mouse intestine. Infect Immun 76: 1143-1152.
112. Cariss SJ, Constantinidou C, Patel MD, Takebayashi Y, Hobman JL, et al. (2010) YieJ (CbrC) mediates CreBC-dependent colicin E2 tolerance in Escherichia coli. J Bacteriol 192: 3329-3336.
113. Gillor O, Giladi I, Riley MA (2009) Persistence of colicinogenic Escherichia coli in the mouse gastrointestinal tract. BMC Microbiol 9: 165.
114. Stephenson K, Hoch JA (2002) Two-component and phosphorelay signal-transduction systems as therapeutic targets. Curr Opin Pharmacol 2: 507-512.
115. Kenney LJ (2002) Structure/function relationships in OmpR and other winged-helix transcription factors. Curr Opin Microbiol 5: 135-141.
116. Shrivastava R, Ghosh AK, Das AK (2007) Probing the nucleotide binding and phosphorylation by the histidine kinase of a novel three-protein two-component system from Mycobacterium tuberculosis. FEBS Lett 581: 1903-1909.
117. Hilliard JJ, Goldschmidt RM, Licata L, Baum EZ, Bush K (1999) Multiple mechanisms of action for inhibitors of histidine protein kinases from bacterial two-component systems. Antimicrob Agents Chemother 43: 1693-1699.
118. Stephenson K, Hoch JA (2004) Developing inhibitors to selectively target two-component and phosphorelay signal transduction systems of pathogenic microorganisms. Curr Med Chem 11: 765-773.
119. Gotoh Y, Eguchi Y, Watanabe T, Okamoto S, Doi A, et al. (2010) Two-component signal transduction as potential drug targets in pathogenic bacteria. Curr Opin Microbiol 13: 232-239.
120. Bourret RB Receiver domain structure and function in response regulator proteins. Curr Opin Microbiol 13: 142-149.
121. Yamauchi K, Tomita M, Giehl TJ, Ellison RT, 3rd (1993) Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment. Infect Immun 61: 719-728.
122. Orsi N (2004) The antimicrobial activity of lactoferrin: current status and perspectives. Biometals 17: 189-196.
123. Bellamy W, Takase M, Wakabayashi H, Kawase K, Tomita M (1992) Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. J Appl Bacteriol 73: 472-479.
124. Di Biase AM, Tinari A, Pietrantoni A, Antonini G, Valenti P, et al. (2004) Effect of bovine lactoferricin on enteropathogenic Yersinia adhesion and invasion in HEp-2 cells. J Med Microbiol 53: 407-412.
125. Tian H, Maddox IS, Ferguson LR, Shu Q Influence of bovine lactoferrin on selected probiotic bacteria and intestinal pathogens. Biometals 23: 593-596.
126. de Bortoli N, Leonardi G, Ciancia E, Merlo A, Bellini M, et al. (2007) Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol 102: 951-956.
127. Artym J, Zimecki M (2005) [The role of lactoferrin in the proper development of newborns]. Postepy Hig Med Dosw (Online) 59: 421-432.
128. Tang Z, Yin Y, Zhang Y, Huang R, Sun Z, et al. (2009) Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d. Br J Nutr 101: 998-1005.
129. Nicolas P (2009) Multifunctional host defense peptides: intracellular-targeting antimicrobial peptides. FEBS J 276: 6483-6496.
130. Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, et al. (2001) Global analysis of protein activities using proteome chips. Science 293: 2101-2105.
131. Natale DA, Shankavaram UT, Galperin MY, Wolf YI, Aravind L, et al. (2000) Towards understanding the first genome sequence of a crenarchaeon by genome annotation using clusters of orthologous groups of proteins (COGs). Genome Biol 1: RESEARCH0009.
132. Blake JA, Harris MA (2002) The Gene Ontology (GO) project: structured vocabularies for molecular biology and their application to genome and expression analysis. Curr Protoc Bioinformatics Chapter 7: Unit 7 2.
133. Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M (2012) KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res 40: D109-114.
134. Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, et al. (2012) The Pfam protein families database. Nucleic Acids Res 40: D290-301.
135. Iyer R, Williams C, Miller C (2003) Arginine-agmatine antiporter in extreme acid resistance in Escherichia coli. J Bacteriol 185: 6556-6561.
136. Sun Y, Fukamachi T, Saito H, Kobayashi H (2011) ATP requirement for acidic resistance in Escherichia coli. J Bacteriol 193: 3072-3077.
137. Preston A, Maskell D (2001) The molecular genetics and role in infection of lipopolysaccharide biosynthesis in the Bordetellae. J Endotoxin Res 7: 251-261.
138. Yethon JA, Whitfield C (2001) Lipopolysaccharide as a target for the development of novel therapeutics in gram-negative bacteria. Curr Drug Targets Infect Disord 1: 91-106.
139. Raetz CR, Reynolds CM, Trent MS, Bishop RE (2007) Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem 76: 295-329.
140. Bermingham A, Derrick JP (2002) The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery. Bioessays 24: 637-648.
141. Levy C, Minnis D, Derrick JP (2008) Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand recognition and mechanism of sulfonamide resistance. Biochem J 412: 379-388.
142. Bhabha G, Tuttle L, Martinez-Yamout MA, Wright PE (2011) Identification of endogenous ligands bound to bacterially expressed human and E. coli dihydrofolate reductase by 2D NMR. FEBS Lett 585: 3528-3532.
143. Schnell JR, Dyson HJ, Wright PE (2004) Structure, dynamics, and catalytic function of dihydrofolate reductase. Annu Rev Biophys Biomol Struct 33: 119-140.
144. Benkovic SJ, Fierke CA, Naylor AM (1988) Insights into enzyme function from studies on mutants of dihydrofolate reductase. Science 239: 1105-1110.
145. Penner MH, Frieden C (1987) Kinetic analysis of the mechanism of Escherichia coli dihydrofolate reductase. J Biol Chem 262: 15908-15914.
146. Onishi HR, Pelak BA, Gerckens LS, Silver LL, Kahan FM, et al. (1996) Antibacterial agents that inhibit lipid A biosynthesis. Science 274: 980-982.
147. Durr UH, Sudheendra US, Ramamoorthy A (2006) LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 1758: 1408-1425.
148. Viola RE (2001) The central enzymes of the aspartate family of amino acid biosynthesis. Acc Chem Res 34: 339-349.
149. Viola RE, Faehnle CR, Blanco J, Moore RA, Liu X, et al. (2011) The catalytic machinery of a key enzyme in amino Acid biosynthesis. J Amino Acids 2011: 352538.
150. Audia JP, Webb CC, Foster JW (2001) Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria. Int J Med Microbiol 291: 97-106.
151. Castanie-Cornet MP, Penfound TA, Smith D, Elliott JF, Foster JW (1999) Control of acid resistance in Escherichia coli. J Bacteriol 181: 3525-3535.
152. Hu CJ, Song G, Huang W, Liu GZ, Deng CW, et al. (2012) Identification of new autoantigens for primary biliary cirrhosis using human proteome microarrays. Mol Cell Proteomics 11: 669-680.

指導教授

陳健生(Chien-Sheng Chen)

審核日期

2013-7-1

推文