第一、由北方墨點法的分析，可知 TPI1、GPM1、PYK1、PGK1 之表現 皆可同時受血清及藥物之調控，因此可以針對這些基因進行突變分析，瞭 解其在型態、入侵能力及抗藥性之影響。
第二、TPI1 基因在本論文研究下，證實了其基因功能會影響型態變化，
但這是在TR-system 下所得到的結果，而此 gene targeting 之方法，進行單 套基因之破壞及TR-system 調控目標基因過度表現及抑制表現的機制，在研 究上的穩定性，是否能夠完全抑制目標基因、是否會受其他的未知的調控 子所影響等問題仍被探討中，所以如能得到TPI1 null mutant，不僅可作為 此系統的對照，也有利於將來進行藥物敏感性實驗(E-test)，為本研究最終 的目的，瞭解TPI1 基因功能和型態變化及抗藥性的關連性。
第六 第 六章 章、 、參 參考 考文 文獻 獻
孔祥琪、陳宜君，90 年。全身性抗黴菌藥物治療的最新進展 全身性抗黴菌 藥物治療的最新進展
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Standard Name
Systemic Name
Molecular
Function Mutant phenotype References
Homozygous null
Heterozygous null
Conditional ERG1 orf19.406 squalene
monooxygenas
e activity Inviable
Inviable(Inferred)
Viable 1.Viable 2.Hyphal growth abnormal 3.Slow growth
4.Drug susceptibility altered 5.Protein localization abnormal
(Favre and Ryder, 1997;
Pasrija, et al., 2005)
Unknown/unspecified ERG2 orf19.6026 C-8 sterol
isomerase activity
1. Viable
2. Drug susceptibility altered 3. Plasma membrane abnormal
(Pierson, et al., 2004a)
Homozygous null Heterozygous null
Unknown/unspecified Multiple ERG3 orf19.767 C-5 sterol
desaturase
activity 1.Viable
2. Drug susceptibility altered
3. Protein activity abnormal
4. Hyphal growth abnormal
5. Virulence defect
1.Viable 2. Wild-type drug sensitivity
1. Viable
2. Drug susceptibility altered
3. Plasma membrane abnormal
1. Viable
2. Drug susceptibility altered
(Chau, et al., 2005; Miyazaki, et al., 1999;
Nolte, et al., 1997; Pierson, et al., 2004a;
Sanglard, et al., 2003b)
ERG4 orf19.5379 similar to sterol C-24 reductase
(Lamb, et al., 1999; Uhl, et al., 2003)
Unknown/unspecified ERG5 orf19.5178 C-22 sterol
desaturase activity
Filamentous growth abnormal Homozygous null
ERG6 orf19.1631 sterol 24-C-methyltra nsferase activity
1. Viable
2. Drug susceptibility altered 3. Plasma membrane abnormal
(Jensen-Pergake s, et al., 1998)
ERG7 orf19.1570 lanosterol synthase activity
(Kelly, et al., 1990; Roessner, et al., 1993) Homozygous
null
Heterozygous null
Unknown/
unspecified
Multiple Overexpression Point ERG11 orf19.922 1.drug binding
2. sterol
Viable Drug susceptibility altered Homozygous null
ERG24 orf19.1598 delta14-sterol reductase
activity 1. Viable
2.Virulence defect
3.Hyphal growth abnormal
(Jia, et al., 2002)
4.Slow growth
5.Drug susceptibility altered ERG25 orf19.3732 C-4
methylsterol oxidase activity
(Marichal, et al., 1999)
Homozygous null (inferred) Depletion ERG26 orf19.2909 C-3 sterol
dehydrogenase (C-4 sterol decarboxylase) activity
Inviable Inviable
(Aaron, et al., 2001)
Homozygous null (inferred) Heterozygous null Depletion ERG27 orf19.3240 3-keto sterol
reductase activity
Inviable Viable 1. Inviable
2. Slow growth
(Bard, et al., 2005; Pierson, et al., 2004b)
表一、白色念珠菌之麥角固醇生合成基因功能整理表
（資料來源： http://www.candidagenome.org/）
表二、醣解酵素基因分別於 YPD＋goat serum (＋S)及 YPD＋Drug 環境中的表現 (＋D：miconazole)，
於 37℃培養下萃取所得 RNA 進行之北方墨點法結果
（符號↑表示 mRNA 偵測表現量大於 SC5314；↓表示小於 SC5314 內的表現量；＝ 表示等於 SC5314 內表現量；
箭頭多寡表示差異量程度）
1 TGTCAATCTA CATAGAGGAG TAGAACGGAT GTAAAGGAAC GGAATATGGA --- 51 ATATGTAATA GTAAAACTCA AAACGTGTGA AACCCAACTC CATAGGCTAA --- 101 AAATAAACCG ATCTTCGGAT AGGATAGGGG ATGAGGTGGT GGTGGGGGAC --- 151 AGAGGACGGG AAAAATTAAT GCGAGAAAGA AAAAAAGCAA AACCGTAAGG --- 201 CGGCAAGAAA GAAAAAAAGA AAAAAGAAAT TTAGACTTTT TTCTGTCGTC --- 251 GTCGTTCCCA TCTGATATAA AACTTGTATT GTATTGTAAC ATCGTTCCCA --- 301 TCGTACCTTT TACTTAAGTG AAATATAAAA AAAATCCGAT GTGCAGGAAT --- 351 GCAATTGTTT TGCGATATTA TTATTTTCAG CATCCCTCTA ATCTAAGAAA --- 401 TACTTTGTAG CCATAGGAAG ACTACGCGAG ACCACACTTG CATATACATA --- 451 CAAACTTCTT CTGTTTTTTT TTGTATTAAA CTTCCTTCAA AACTACTTGT --- 501 TAAGCTTTTT TTTCTTCCAC CTATTTTGAT AGATTTTTTT CATTTTCATT --- 551 TTCATAGTAG TTGTTTTGAA ATTGGAAAAA AAAAAAACAT TCAATAATAA --- 601 ACATAGTGGA GTGGTGTTAC TTTCGTTTAA GTATTCCTTT GCATTTGCTA --- 651 AAATCTGATT TATATATTTA TTCAAGTGTT TGGCTTTAAT CTTTGCTATT --- 701 AATATAATTT CTGCTTTTTT CTTTTCTTTA ATAAACCATA GCAGATAATC --- 751 CCTTTTTTTT CATTAAAATC AACTAAGGTC AACCTTCCCA TCACATTACT --- 801 GCTTACTTTG AGAGGTTCTT TAACAGTTTC CCATTTTCCT TCCAATTGTT --- 851 AATCCTTGCT CATTATCATA TCTTGACCTA AGATTCCTAC AATCTAGATA --- 901 TCTTTGGACA TTCTATTCCC TTCCCATTTC TTTCCCTATT GTGCATATAA ---
951 GTTCAATCTT TTTTTCTTTC TTTCGGATTC GGTTTAGCCA ATTTTACTAC --- 1001 CATGGATATC GTACTAGAAA TTTGTGACTA TTATCTTTTT GATAAAGTTT ---
1051 ATGCTGATGT TTTCCCTAAA GATGGTGCTG TTCATGAATT TTTGAAACCA TACGACTACA AAAGGGATTT CTACCACGAC AAGTACTTAA AAACTTTGGT 1101 GCTATACAAT CATTTTCACA AATAGATTTC CCAAGTCTCC CAAATTTGGA CGATATGTTA GTAAAAGTGT TTATCTAAAG GGTTCAGAGG GTTTAAACCT 1151 TTCATTTGAT ACAAATTCTA CTTTGATTTC TTCAAATAAT TTCAATATTA AAGTAAACTA TGTTTAAGAT GAAACTAAAG AAGTTTATTA AAGTTATAAT 1201 GTAATGTTAA CCCAGCAACT ATTCCAAGTT ATTTATTTTC TAAAATTGCT CATTACAATT GGGTCGTTGA TAAGGTTCAA TAAATAAAAG ATTTTAACGA 1251 AGTTATCAAG ATAAATCAGA AATTTATGGA TTAGCTCCTA AATTTTTCCC TCAATAGTTC TATTTAGTCT TTAAATACCT AATCGAGGAT TTAAAAAGGG
表三、 Efg1 之 consensus binding sequence ( 5’- CANNTG-3’) 和 ERG3 之 promoter region(-1050～-1 of ERG3 ORF )比對的結果。結果顯示：ERG3 ORF 之上游約一千左右個核苷酸序列中沒有 5’- CANNTG-3’的序列。
註：表中標號1 核苷酸至 1050 個核苷酸為 ERG3 ORF 之上游區域。標號 1051~1053 核苷酸為 ERG3 基因轉錄之起始密碼；編號 1051~1300 核苷酸 為ERG3 ORF 之一部分。
transcription start
1 GGTAAGAATT GCCAACATAA CCTTACCTAT TTATATAGAT CAGATTCAAA
1 GGTAAGAATT GCCAACATAA CCTTACCTAT TTATATAGAT CAGATTCAAA