請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75442完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.author | Yi－Pin Lin | en |
| dc.contributor.author | 林宜屏 | zh_TW |
| dc.date.accessioned | 2021-07-01T08:13:14Z | - |
| dc.date.available | 2021-07-01T08:13:14Z | - |
| dc.date.issued | 2003 | |
| dc.identifier.citation | [1] Walsh, C. (2000) Molecular mechanisms that confer antibacterial drug resistance. Nature 406, 775-781. [2] Robyt, J. (1998) in Essentials of carbohydrate chemistry, chapter 10, pp 305-3 18, Springer-Verlag, NY [3] Spratt, B. G, and Cromic, K. D. (1988) Penicillin-binding proteins of gram-negative bacteria. Rev. Infect. Dis. 10, 699-711. [4] Williams, D. H. (1996) The glycopeptide story-how to kill the deadly “superbugs”. Natl. Prod. Rep. 13, 469-477. [5] Brisson-Noel, A., Tricu, Cuot,P., and Courvalin, P. (1988) Mechanism and action of spiramycin and other macrolides. J. Abntimicrob. Chemother. 22 (Suppl. B),13-23. [6] Chopra, I. (1985) in The tetracyclins, Handbook of Experimental Pharmacology 78, (eds Hlavaka, J. J. & Boothe, J. H.) 317-392. [7] Fourmy, D., Recht, M. I., Blanchard, S. C., and Puglisi, J.D. (1996) Structure of the A site of the Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science 274, 1371-1376. [8] Kloss, P., Xiong, L., Shinabarger, D. L., and Mankin, A.S. (1999) Resistance of mutations in 23S rRNA identify the site of action of the protein synthesis inhibitor linezolid in the ribosomal peptidyl transferase center. J. Mol. Biol. 294, 93-101. [9] Shen, L.L. (1993) in Quinolone AntibacterialAgents, 2nd edn (eds Hooper, D. C. & Wolfson, J. S.) 77 (American Society for Microbiology, Washington DC). [10] Davies, J. (1996) Bacteria on the rampage. Nature 383, 2 19-220. [11] Arthur, M., and Courvalin, P. (1993) Genetics and mechanisms of glycopeptide resistance in enterococci. Antimicrob. Agents Chemother 37, 1563-1571. [12] Walsh, C, Fisher, S. L., Park, I. S., Prahalad, M., and Wu, Z. (1996) Bacterial resistance to vancomycin: five genes and one missing hydrogen bond tell the story. Chem. Biol. 3, 21-28. [13] Bugg, T. D. H. et al. (1991) Molecular basis for vancomycin resistance in Enterococcus faecium, BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry 30,10408-10415. [14] Knowles, J. R. (1985) Penicillin resistance: the chemistry of beta-lactamase inhibition. Acc. Chem. Res. 18, 97-105. [15] Levy, S .B. (1992) Active efflux mechanisms for antimicrobial resistance. Antimicrob. Agents Chemother 36, 695-703. [16] Paulsen, I. T., Brown, M. H., and Skurray, R.A. (1996) Proton-dependent multidrug efflux systems. Microbiol. Rev. 60, 575-608. [17] Ross, J. et al. (1990) Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super gene family. Mol. Microbiol. 4, 1207-1214. [18] Philippon, A., Labia, R., and Jacoby, G (1985) Extended spectrum beta-lactamases. Antimicrob. Agents Chemother 28, 302-307. [19] Shaw, K. J., Rather, P. N., Hare, S. R., and Miller, G. H. (1993) Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Micro biol. Rev. 57, 138-163. [20] Mah, T.-F., and O’Toole, G. A. (2001) Mechanisms of biofilm resistance to antimicrobial agents. Trends in Microbiology 9, 34-39. [21] Govan, J. R., and Deretic, V. (1996) Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Micro biol. Rev. 60,539-574. [22] Drenkard, E., and Ausubel, F. M. (2002) Pseudomonas biofllm formation and antibiotic resistance are linked to phenotypic variation. Nature 416, 740-743. [23] O’toole, G A. (2002) A resistance switch. Nature 416, 695-696. [24] Robichon, D., Gouin, E., Debarbouille, M., Cossart, P., Cenatiempo, Y., and Hechard, Y. (1997) The rpoN (sigma54) gene from Listeria monocytogenes is involved in resistance to mesentericin Y105, an antibacterial peptide from Leuconostoc mesenteroides. J Bacteriol. 179, 7591-7594. [25] Stone, K. J., and Strominger, J. L. (1971) Mechanism of action of bacitracin: complexation with metal ion and C55-isoprenyl pyrophosphate. Proc. Natl. Acad. Sci. USA 68, 3223-3227. [26] Storm, D. R., and Strominger, J. L. (1973) Complex formation between bacitracin peptides and isoprenyl pyrophosphates. J. Biol. Chem. 248, 3940-3945. [27] Rieber, M., Imaeda, T., and Cesari, I. M. (1969) Bacitracin action on membranes of Mycobacteria. J. Gen. Microbiol. 55, 155-159. [28] Makinen, K. K. (1972) Inhibition by bacitracin of some hydrolytic enzymes. Int. J. Protein. Res. 4, 2 1-28. [29] Schechter, N., Momose, K., and Rudney, H. (1972) The effect of bacitracin and Ca2+ on the formation of polyprenylpyrophosphates and their incorporation into ubiquinone precursors in mammalian and bacterial systems. Biochim. Biophys. Res. Comm. 48, 833-839. [30] Giraud, E., Cloeckaert, A., Kerboeuf, D., and Chaslus-Dancla, E. (2000) Evidence for active efflux as the primary mechanism of resistance to ciprofloxacin in Salmonella enterica serovar typhimurium. Antimicrob Agents Chemother 44,1223-1228. [31] Liu, C. E., and Ames, G F. (1997) Characterization of transport through the periplasmic histidine permease using proteoliposomes reconstituted by dialysis.J.Biol. Chem. 272, 859-866. [32] O’Farrell, P. H. (1975) High resolution two-dimentional electrophoresis of proteins. J. Biol. Chem. 250, 4007-4021. [33] Gorg, A. C., Obermaier, G, Boguth, A., Harder, A., Scheibe, B., Wildgruber, R., and Weiss, W. (2000) The current state of two-dimentional electrophoresis with immobilized pH gradients. Electrophoresis 6, 1037-1053. [34] Shevchenko, A., Wilm, M., Vorm, O., and Mann, M. (1996) Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68,850-858. [35] Scheler, C., Lamer, S., Pan, Z., Salnikav, J., and Jungblut, P. (1998) Peptide mass fingerprint sequence coverage from differently stained protein on two-dimentional electrophoresis patterns by matrix assisted laser desorption/ionization mass spectroscopy (MALDI-MS). Electrophoresis 19, 918-927. [36] Davidson, A. L., and Nikaido, H. (1990) Overproduction, solubilization, and reconstitution of the maltose transport system from Escherichia coli. J. Biol. Chem. 265, 4254-4260. [37] YadL: NC 000913, putative fimbrial protein [gi:16127994]. [38] YehB: NP 416612, putative outer membrane protein [gi:16130047]. [39] Ybiw: NC_000913, putative formate acetyltransferase [gi:16127994]. [40] Wissenbach, U., Six, S., Bongaerts, J., Temes, D., Steinwachs, S., and Unden, G (1995) A third periplasmic transport system for L-arginine in Escherichia coli:molecular characterization of the artPQIMJ genes, arginine binding and transport Molecular Microbiology 17, 675-686. [41] Kato, A., Ohnishi, H., Kamamoto, K., Furuta, E., Tanabe, H., and Utsumi, R. (2000) Transcription of emrKY is regulated by the EvgA/EvgS two-component system in Escherichia coli K-12. Biosci. Biotechnol. Biochem. 64, 1203-1209. [42] Erbeznik, M., Ray, M., Dawson, K. A., and Strobel, H. J. (1998) Xylose transporter by the anaerobic thermophilic Thermoanaerobacter ethanolicus and the characterization of a D-xylose-binding protein. Current Microbiology 37,295-300. [43] Soto, G. E., and Hultgren, S. J. (1999) Bacterial adhesins: common themes and variations in architecture and assembly. J Bacteriol. 181, 1059-1071. [44] Toyama, H., Chistoserdova, L., and Lidstrom, M. E. (1997) Sequence analysis of pqq genes required for biosynthesis of pyrroloquinoline quinone in Methylobacterium extorquens AM1 and the purification of a biosynthetic intermediate. Microbiology 143, 595-602. [45] Abadjieva, A., Patel, J., Webb, M., Zinkevich, V., and Firman, K. (1993) A deletion mutant of the type IC restriction endonuclease EcoRl24l expressing a novel DNA specificity. Nucleic Acids Res. 21, 4435-4443. [46] Chaudhuri, B. S., Bhakta, S., Barik, R., Basu, J., Kundu, M., and Chakrabarti, P. (2002) Overexpression and functional characterization of an ABC transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis. Biochem. J.367, 279-285. [47] Putman, M., van Veen, H. W., and Konings, W. N. (2000) Molecular properties of bacterial multidrug transporters. Microbiol. Mol. Biol. Rev. 64, 672-693. [48] Bambeke, F., Balzi, E., and Tulkens, P. M. (2000) Antibiotic efflux pumps. Biochem. Pharm. 60, 457-470. [49] Erbeznik, M., Strobel, H. J., Dawson, K. A., Jones, C. R. (1998) The D-xylose-binding protein, xylF, from Thermoanaerobacter ethanolicus 39E:cloning, molecular analysis, and expression of the structure gene.J. Bacteriol. 180,3570-3577. [50] Lee, S. H., Angelichio, M. J., Mekalanos, J. J., and Camilli, A. (1998) Nucleotide sequence and spatiotemporal expression of the Vibrio cholerae vieSAB genes during infection. J Bacteriol. 180, 2298-305. [51] Kazama, H., Kizu, K., Iwasaki, M., Hamashima, H., Sasatsu, M., and Arai, T. (1996) A new gene, aadA2b, encoding an aminoglycoside adenylyltransferase, AAD(3‘)(9), isolated from integron InC in Pseudomonas aeniginosa. Microbios 86, 77-83. [52] Christina, M., Collis and Ruth M., Hall (1992) Gene cassettes from the insert region of integrons are excised as covalently closed circles. Molecular Microbiology 6, 2875-2885. [53] Van Veen, H. W., Venema, K., Boihuis, H., Oussenko, I., Kok, j., Poolman, B., Driessen, A. J. M., and Konings, W. N. (1996) Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc. Natl. Acad.Sci. USA 93, 10668-10672. [54] Kido, N., Sugiyama, T., Yokochi, T., Kobayashi, H., Okawa, Y. (1998) Synthesis of Escherichia coli 09a polysaccharide requires the participation of two domains of WbdA, a mannosyltransferase encoded within the wb* gene cluster. Molecular Microbiology 27, 1213-1221. [55] Van der Rest, M. E., Frank, C., Molenaar, D. (2000) Foundation of the membrane-associated and cytoplasmic malate dehydrogenase in the citric acid cycle of Escherichia coli. J. Bacteriol. 182, 6892-6899. [56] McClean, K. H., Winson, M. K., Fish, L., Taylor, A., Chhabra, S. R., Camara, M., Daykin, M., Lamb, J. H., Swift, S., Bycroft, B. W., Stewart, G, and Williams, P. (1997) Quorum sensing and Chromobacterium violaceum: exploitation of violacein production and inhibition for the detection of N-acylhomoserine lactones. Microbiology 143, 3703-3711. [57] Geisenberger, P., Givskov, M., Riedel, K., Hoiby, N., Tummler, B., and Eberl, L. (2000) Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis. FEMS Microbiol. Lett. 184,273-278. [58] More, M. I., Finger, D., Stryker, J. L., Fuqua, C., Eberhard, A., and Winans, S. C. (1996) Enzymatic synthesis of a quorum sensing autoinducer using defined substrates. Science 272, 1655-1658. [59] Chen, X., Schauder, S., Potier, N., Dorsselaer, A. V., Pelczer, I., Bassler, B. L., and Hughson, F. M. (2002) Structural identification of a bacterial quorum-sensing signal containing boron. Nature 415, 545-549. [60] Schembri, M. A., and Klemm, P. (2001) coordinate gene regulation by fimbriae-induced signal transduction. EMBO J. 20, 3074-3081. [61] Dodson, K. W., Jacob-Dubuisson, F., Striker, R. T., and Hultgren, S. J. (1993) Outer-membrane Papc molecular usher discriminatedly recognizes periplasmic chaperone-pilus subunit complexes. Proc. Natl. Acad. Sci. USA 90, 3670-3674. [62] Jacob-Dubuisson, F., Striker, R., and Hultgren, S. J. (1994) Chaperone-assisted self-assembly of pili independent of cellular energy. J. Biol. Chem. 269,12447-12455. [63] Saulino, E. T., Thanassi, D. G, Pinkner, J. S., and Hultgren, S. J. (1998) Ramifications of kinetic partitioning on usher-mediated pilus biogenesis. EMBO J.17, 2177-2185. [64] Saulino, E. T., Bullitt, E., and Hultgren, S. J. (2000) Snapshots of usher-mediated protein secretion and ordered pilus assembly. Proc. Natl. Acad. Sci. USA 97,9240-9245. [65] Nishino, K., and Yamaguchi, A. (2001) Overexpression of the response regulator evgA of the two-component signal transduction system modulates multidrug resistance conferred by multidrug resistance transporters. J Bacteriol. 183,1455-1458. [66] Konz, D., Klens, A., Schorgendorfer, K., and Marahiel, M. A. (1997) The bacitracin biosynthesis operon of Bacillus licheniformis ATCC 10716: molecular characterization of three multi-modular peptide synthetases. Chemistry & Biology4, 927-937. [67] Podlesek, Z., Comino, A., Herzog-Velikonja, B., Zgur-Bertok, D., Komel, R., and Grabnar, M. (1995) Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Molecular Microbiology 16, 969-976. [68] Cain, B. D., Norton, P. J., Eubanks, W., Nick, H. S., and Allen, C. M. (1993) Amplification of the bacA gene confers bacitracin resistance to Escherichia coli. J Bacteriol. 175, 3784-3789. [69] J.Gustafson, A. Strassle, H. Hachier, F.H. Kayser and B.Berger-bachi (1994) The femC locus of staphylococcus aureus required for methicillin resistance includes the glutamine synthetase operon. Journal of Bacteriology 176(5), 1460-1467 [70] K.F. Whelan, R.K. Sherburne and D.E. Taylor (1997) Characterization of a region of the IncHI2 plasmid R478 which protects Escherichia coli from toxic effects specified by components of the tellurite, phage, and colicin resistance cluster. Jouranl of Bacteriology 178(1), 63-71 [71] Gazouli M, Tzouvelekis LS, Vatopoulos AC, Tzelepi E.(1998) Transferable class C beta-lactamases in Escherichia coli strains isolated in Greek hospitals and characterization of two enzyme variants (LAT-3 and LAT-4) closely related to Citrobacter freundii AmpC beta-lactamase. JAntimicrob Chemother 42(4), 419-425. [72] R.C. Sandlin and D.C. Stein (1994) Role of phosphoglucomutase in lipioligisaccharide biosynthesis in Neiseria gonorrhoeae Journal of Bacteriology176(11), 2930-2937 [73] F.J. Dubuisson, J. Pinkner, Z. Xu, R. Striker, A. Padmanhaban and S.J. Hultgren(1994) PapD chaperone function in pilus biogenesis depends on oxidant and chaperone-like activities of dsbA. Proc. Natl. Acad. Sci. USA 91, 11552-11556 [74] F.E. Dailey and H.C. Berg (1993) Mutant in disulfide bond formation that disrupt flagellar assembly in Escherichia coli Proc. Natl. Acad. Sci. USA 90, 1043-1047 [75] P. Genevaux, P. Bauda, M.S. Dubow, B. Oudega (1999) Identification of Tnl0 insertions in the dsbA gene affecting Escherichia coli bioflim formation. FEMS Microbiology Letters 173, 403-409 [76] M.R. Warne, J.M. Varley, G.J. Boulnois and M.G Norton (1990) Identification and characterization of a gene that controls colony morphology and auto-aggregation in Escherichia coil K12. Journal of General Microbiology 136,455-462 [77] B. Gorke and B. Rak (2001) Effcient transcriptional antitermination from the Escherichia coil cytoplasmic membrane. Journal of Molecular Biology308, 13 1-145 [78] C. Delorme, S.D. Ehrlich and P. Renault (1992) Histidine Biosynthesis Genes in Lactococcus latis subsp. Latis. Journal ofBacteriology 174(20) 657 1-6579 [79] Song WJ, Jackowski S. (1992) Cloning, sequencing, and expression of the pantothenate kinase (coaA) gene of Escherichia coil. Jounal of Bacteriololgy.174(20) 6411-6417. [80] De Veaux LC, Clevenson DS, Bradbeer C, Kadner RJ. (1986) Identification of the btuCED polypeptides and evidence for their role in vitamin B12 transport in Escherichia coli. Journal of Bacteriology. 167(3), 920-7. [81] C.C.Liao, K.C. Hsiao, Y.W. Liu, P.H. Liang, H.S. Yuen, K.F. Chak (2001) Processing of Dnase Domain during translocation of colicin E7 across the membrane of Escherichia coli. Biochemical and Biophyisical Research Communication 284, 556-562 [82] C. Kirkpatrick, L.M. Maurer, N.E. Oyelakin, Y.N. Yoncheva, R.Maurer and J.L. Slonczewski (2001) Acetate and formate stress : opposite responses in the proteome of Escherichia coli. Journal of Bacteriology 183(2 1) 6466-6477 [83] E.E. Wyckoff, A.M. Valle, S.L. Smith and S.M. Payne (1999) Amultifunctional ATP-binding cassette transporter system from Vibrio cholerae transports vibriobactin and enterobactin. Journal of Bacteriology 181(24) 7588-7596 [84] Miles JS, Guest JR. (1984) Nucleotide sequence and transcriptional start point of the phosphomannose isomerase gene (manA) of Escherichia coli. Gene 32, 41-8. [85] Bouvier J, Richaud C, Richaud F, Patte JC, Stragier P. (1984) Nucleotide sequence and expression of the Escherichia coli dapB gene. J Biol Chem. 259(23):14829-34. [86] Coulthurst, S. J., Whitehead, N. A., Welch, M., and Salmond, G P.C. (2002) Can boron get bacteria talking Trends Biochem. Sci. 27, 217-219. [87] Swift, S., Throup,J. P., Williams, P., Salmond, G P.C., and Stewart, (3. S.A.B. (1996) Quorum sensing: a population-density component in the determination of bacterial phenotype. Trends Biochem. Sci. 21, 214-219. [88] Wirth, R., Muscholl, A., and Wanner, G (1996) The role of pheromones in bacterial interactions. Trends Microbiol. 4, 96-103. [89] Fuqua, C., Winans, S. C., and Greenberg, E. P. (1996) Census and consensus in bacterial ecosystems: the LuxR-LuxI family of quorum-sensing transcriptional regulators. Annu. Rev. Microbiol. 50, 727-751. [90] Riedel, K., Hentzer, M., Geisenberger, O., Huber, B., Steidle, A., Wu, H., Hoiby, N., Givskov, M., Molin, S., and Eberl, L. (2001) N-acylhomoserine-lactone-mediated communication between Pseudomonas aeruginosa and Burkholderia cepacia in mixed biofilms. Microbiology 147,3249-3262. [91] Huisman, G W., and Kolter, R. (1994) Sensing starvation: a homoserine lactone-dependent signaling pathway in Escherichia coli. Science 265, 537-539. [92] Wolfe, A. J., Chang, D. E., Walker, J. D., Seitz-Patridge, J. E., Vidaurri, M. D., Lange, C. F., Pruss, B. M., Henk, M. C., Larkin, J. C., Conway, T. (2003) Evidence that acetyl phosphate functions as a global signal during biofilm development. Mol Microbiol. 48, 977-988. [93] Walters III, M. C., Roe, F., Bugnicourt, A., Franklin, M. J., and Stewart, P. S.(2003) Contributions of Antibiotic Penetration, Oxygen Limitation, and Low Metabolic Activity to Tolerance of Pseudomonas aeruginosa Biofilms to Ciprofloxacin and Tobramycin. Antimicrobial Agents Chemotherapy 47, 317-323. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/75442 | - |
| dc.description.abstract | 枯草桿菌素是藉著和細菌胞壁合成必需的八異戊二烯焦磷酸相結合以抑 制細菌生長的常用抗生素。先前已發現八異戊二烯醇激?可造成細菌對枯 草桿菌素的抗藥性。在此論文我們使用系統生物學方法（包括跳躍子基因 破壞及蛋白質體學）來研究細菌對抗生素抗性及感受性之機制。跳躍子基 因破壞可用來篩選對枯草桿菌素具抗性及感受性之變種株。發現包括去掉 yadL ( putative fimbrial protein ) , artP ( ATPase of arginine transporter ) , evgS ( two－component system ) ,b145l ( membrane receptor for ion transport ) , b1121 ( virulence factor) , b1809 ,b1810,ybiW(putative formate acetyltransferase）及yehB ( Pilus usher protein ）之變種株對枯草桿菌素 有較高桿受性。而去掉fimA ( major type subunit fimbrin ) ,pqqL(putative zinc peptidase ) ，xylF ( xylose binding protein transport system )及 hsdM ( a DNA methylase）導致較高抗性。這些結果顯示 XylFGH及ArtPQIM 分別可將枯草桿菌素吸入及排出。而 transporter assay 的確證明如此。 YehB是細菌表面纖毛疏密的決定因數，可決定biofilm的形成及對抗生 素的抗藥性。更進一步我們也用蛋白質體學研究得到 biofilm 的形成及 藥性基因活化的關聯。YehB 高度表現的菌種可形成 biofilm ，並?生 較多的 AadAI ( aminoglycoside adenylyltransferase ) , mdh ( malate dehyrogenase ) , ydjA , yehZ( putative transport system permease protein ） 和 wbdC ( mannosyl transferase ）及較少的 YbfL（putative receptor ) , YgfD( putative nucleotide－binding protein ）和 YgfP。如預期，此株對 kanamycin 呈現較高的抗性乃因其可用 AadA1 修飾此抗生素。 對付細菌細胞壁及細胞膜的抗生素可造成 biofilm 形成。而在枯草桿菌素 處理過的大腸桿菌可分泌費洛蒙到胞外造成 biofilm 形成。根據質譜儀、 核磁共振光譜儀及氣相層析質譜儀得知，此物質為具備豆蔻酸（14 :0）、 棕櫚酸（16 : 0）、棕櫚烯酸（16 : 1）、正十七烷酸（17 : l）及油酸（18 : 1） 及脂肪酸鏈的分子，其分子量為 1221.8 Da 。此大腸桿菌DH5分泌而導 致 biofilm 形成之物質完全不同於以往所發現autoinducers 。在培養基加 入 acetate 可增加此費洛蒙的表現量且可使細菌對抗枯草桿菌素的能力增 強說明 acetate 可能是其生合成之先驅。 為了瞭解細菌對外來抗生素的反應，大腸桿菌被枯草桿菌素處理過及未處 理過的膜蛋白或細胞質蛋白分別跑二維膠。在胞膜上有一未知蛋白 B2636 大量表達。其他蛋白包括 GlnA ，TerZ , Bla LAT-4 , EvgA , ManB , B2339 , DsbA , B2636 , BglG, LysR , YcgE , YihW, HisA , CoaA， YfbU , Cof,YqcD and YihS 在被抗生素處理的細胞表現較多。相反的 BtuE , FliY , FepC , ManA, FfoA , YghO , Fba , Gnd , and DapB 表現較少。 | zh_TW |
| dc.description.abstract | Bacitracin is a commonly used antibiotic that inhibits the bacterial cell wall biosynthesis by binding with undecaprenyl pyrophosphate (UPP) and blocking its dephosphorylation into a lipid carrier. Previous study had demonstrated that undecaprenol kinase confers resistant to bacitracin by supplementing the undecaprenyl phosphate. In the present study, the methods of system biologys (transposon gene knockout and 2-D proteomics technicals) were employed to identify other factors, which affect the toxicity of bacitracin as well as other antibiotics to E. coli. The mutant E. coli strains with a single gene disrupted by transposon were selected for increased bacitracin susceptibility and resistance. The removal of the proteins including yadL (putative fimbrial protein), artP (ATPase of arginine transporter), EvgS (two-component system), b1451 (membrane receptor for ion transport), bl121 (virulence factor), b1809, b1810, ybiW(putative formate acetyltransferase), and yehB (pilus usher protein) was found to cause higher sensitivity to bacitracin. On the other hand, disruption of fimA (major type 1 subunit fimbriae), pqqL (putative zinc peptidase), xylF (xylose binding protein transport system), and hsdM (a DNA methylase) resulted in more resistant strains. The ABC-transporters XyIFGH and ArtPQIM may be involved in the influx and efflux of bacitracin and other antibiotics, respectively. The transporter assay indeed confirmed this conclusion.
YehB, the usher protein for pilus assembly, is essential to determine bioflim formation and thus antibiotic resistance. Furthermore, evidences linking bioflim formation and overexpression of antibiotic resistance genes were obtained from 2-D gel proteomic studies. The YehB overexpressed strain with more biofilm formation produced higher level of AadA2 (aminoglycoside adenylyltransferase), Mdh (malate dehydrogenase), YdjA, YehZ (putative transport system permease protein) and WbdC (mannosyl transferase) as well as lower level of YbfL (putative receptor), YgfD (putative nucleotide-binding protein), and YgfP. As expected, this strain showed much higher resistance to kanamycin which can be modified by AdaA2. Furthermore, the antibiotics targeting bacterial cell wall are more likely to induce bioflim formation. Also, a chemical (possibly a pheromone) secreted by the E. coli cells was found to cause formation of bioflim upon bacitracin treatment. Reverse phase silica gel and HPLC purification of the extract from the medium yielded a compound with a molecule mass of 1221.8Da according to mass analysis. Moreover, This compound contains five fatty acid chains, myristic acid, palmitic acid, Palmitoleic acid, heptadecenoic acid and Oleic acid, according to TOF-MS/MS, NMR and GC-MS analysis. This pheromone is structurally different from those autoinducers previously discovered from bacteria. To investigate the bacterial response under stress (antibiotic treatment), the E. coil cells treated with bacitracin at a concentration slightly lower than MIC were collected and the proteins with higher or lower expression level in comparison with the sample from untreated cells were analyzed by using 2-D gel electrophoresis. A putative transcription factor B2636 in the membrane of the treated cells was highly overexpressed. Other proteins including G1nA, TerZ, BlaLAT-4, EvgA, ManB, B2339, DsbA, B2636, Bg1G LysR, YcgE, YihW, HisA, CoaA, YfbU, Cof, YqcD and YihS were expressed at higher quantity and BtuE, FliY, FepC, ManA, FfoA, YgbO, Fba, Gnd, and DapB at lower amount. Their function in response to bacitracin will be further examined. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-01T08:13:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2003 | en |
| dc.description.tableofcontents | ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . 3 ABBREVIATIONS . . . . . . . . . . . . . . . . . . . 8 INTRODUCTION . . . . . . . . . . . . . . . . . . . 10 MATERIALS AND METHODS. . . . . . . . . . 17 RESULTS . . . . . . . . . . . . . . . . . . . . . . . 33 DISCUSSION . . . . . . . . . . . . . . . . . . . . . 48 TABLES . . . . . . . . . . . . . . . . . . . . . 61 FIGURES . . . . . . . . . . . . . . . . . . . . . 68 REFERENCES . . . . . . . . . . . . . . . . . . 101 APPENDICES . . . . . . . . . . . . . . . . . . 116 | |
| dc.language.iso | zh-TW | |
| dc.title | 運用系統生物學研究細菌抗生素抗性及感受性之機制 | zh_TW |
| dc.title | Systems biology approaches to reveal the mechanism of antibiotics resistance and susceptibility | en |
| dc.date.schoolyear | 91-2 | |
| dc.description.degree | 碩士 | |
| dc.relation.page | 123 | |
| dc.rights.note | 未授權 | |
| dc.contributor.author-dept | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
文件中的檔案：
沒有與此文件相關的檔案。
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。