水產養殖業者大多是使用抗生素來治療細菌性疾病，伴隨而來的問題是抗藥性菌株的產生。本研究採集台灣南部地區PCG石斑養殖場與EMD、THOD海鱺箱網養殖場病魚脾肝腎之菌株，以TCBS培養，分別有83%、76%與100%為弧菌；PCG與EMD場分別有13%、24%菌株為完全溶血，而THOD場沒有完全溶血菌株。選取PCG、EMD與THOD場代表菌24、29、6株，測試其對17種抗生素之敏感性，結果顯示PCG場有70%菌株對penicillin、cephazolin與streptomycin具抗藥性，對cephazolin/streptomycin具雙重抗藥性，而抗雙重藥物的菌數隨時間由0%增加至83%。EMD場有70%菌株對streptomycin或furazolidone具抗藥性，對furazolidone/streptomycin具雙重抗藥性，而抗雙重藥物的菌數隨時間由0%增加至60%。THOD場有50%菌株對β-lactam具抗藥性，且100%具cephazolin抗藥性，而有67%菌株對ampicillin/amoxycillin、cephalexin/cephazolin、cephalexin/strepto- mycin、cephazolin/streptomycin 等具雙重抗藥性。進一步選出抗10種以上抗生素之多重抗藥性細菌17株，以抗四環素基因tetB、tetD、tetM、tetS與tetX等五對引子分析，並利用限制酶確認所增幅之產物，本研究發現THOD場之J39-1、J39-2、K26-4、K27-2及PCG場之N18-5及M35-2菌株皆具tetB。EMD場之P19-1、P19-3、P32-1、Q8-3具tetB和tetM，而O2-3具tetS。

Antibiotics are frequently used in aquaculture for the treatment of bacterial diseases. In this study, bacteria were isolated from the spleen, liver and kidney of grouper from PCG and cobia from EMD and THOD in southern Taiwan. All isolates were cultured on TCBS agar, blood agar, and MacConkey agar. The results showed that the isolates from PCG were 83% (20/24) Vibrio and 13% (3/24) β-hemolysis；76% (22/29) Vibrio and 24% (7/29) β-hemolysis from EMD；100% (6/6) Vibrio and none of β-hemolysis from THOD. The bacteria were tested for antibiotics resistance by the disc agar diffusion method. 70% bacteria resisted to penicillin, cephazolin, and streptomycin while double resistance to furazolidone/streptomycin increased to with time from 0% to 83% in PCG. In EMD, 70% bacteria resisted to streptomycin and furazolidone, and double resistance to furazolidone/streptomycin increased with time from 0% to 60%. In THOD, 50% bacteria resisted to β-lactam drugs, 100% bacteria resisted to cephazolin, and 67% bacteria doubly resisted to ampicillin/amoxycillin, cephalexin/cephazolin, cephalexin/streptomycin and cephazolin/streptomycin. Further, the detection of tetB, tetD, tetM, tetS and tetX resistance, tetracycline resistance genes, in the chromosomal DNAs from 17 multiple resistance isolates were performed by PCR. The PCR products were confirmed by digestion of restriction enzymes. The data indicated that J39-1, J39-2, K26-4 and K27-2, strains from THOD, together with N18-5 and M35-2, from PCG, were identified as carrying tetB. From EMD, The tetB and tetM genes were detected in P19-1, P19-3, P32-1 and Q8-3, whereas strain O2-3 carried tetS gene.

謝誌 I
摘要 II
Abstract III
目錄 IV
壹、前言 1
一、 台灣養殖概況 1
二、 台灣石斑養殖現況 2
三、 台灣海鱺養殖現況 3
四、 抗生素之發展 3
五、 抗生素的類型 5
1. β-lactam 5
2. Aminoglycoside 5
3. Macrolide 6
4. Tetracyclines 6
5. Chloramphenicol 6
6. Quinolones 7
六、 抗生素的作用機制 7
1. 抑制細胞壁的合成 7
2. 抑制細胞膜的功能 8
3. 抑制蛋白質合成 8
4. 抑制細菌之主要代謝物 8
5. 抑制核酸合成 9
七、 細菌的抗藥性產生 9
1. 阻止藥物在細菌內累積 9
2. 突變藥物的攻擊區 10
3. 擁有酵素可破壞藥物效能或活性 11
八、 細菌抗藥性的檢驗 11
1. 紙錠瓊脂擴散試驗法 11
2. 稀釋試驗法 12
九、 細菌抗四環素的機制 12
十、 抗四環素之菌株 13
十一、 研究目的 15
貳、材料與方法 16
一、 細菌的採集與分離 16
二、 細菌藥物敏感性試驗 16
三、 特殊培養基篩選與分類 17
1. 特殊培養基TCBS培養基檢測 17
2. 特殊培養基MacConkey agar檢測 17
3. 單一菌落之溶血性試驗 18
四、 細菌形態及生理特性分析 18
1. 革蘭氏染色 18
2. 觸媒試驗(catalase test) 18
五、 細菌胞外產物酵素活性測試 19
1. 細菌胞外產物(extracellular products, ECP) 的製備 19
2. 蛋白質濃度定量(Lowry method) 19
3. 酵素活性測試 (Azo-protein assay) 19
六、 核酸萃取 20
七、 PCR (Polym erase Chain Reaction)反應條件與程序 21
1. PCR增幅(amplification) 21
2. 核酸產物的確認 21
八、 限制性內切酶之分析(Restriction endonuclease analysis) 22
參、結果 23
一、 菌株之採集與分離 23
二、 藥物敏感性試驗 23
1. 不同時間採集PCG場菌株之檢測 23
2. 不同時間採集EMD場菌株之檢測 25
3. THOD場菌株之檢測 26
4. 於不同時間採集EMD場水樣菌株之檢測 27
三、 雙重抗藥性 28
1. 不同時間採集PCG場菌株之雙重抗藥性 28
2. 不同時間採集PCG場菌株之雙重敏感性 31
3. 不同時間採集EMD場菌株之雙重抗藥性 32
4. 不同時間採集EMD場菌株之雙重敏感性 33
5. THOD場之雙重抗藥性 35
6. THOD場之雙重敏感性 35
四、 多重抗藥性細菌分離與藥物敏感性試驗 35
五、 抗四環素基因之偵測 36
六、 以限制性酶確立抗四環素基因之類型 37
肆、討論 39
伍、參考文獻 45
陸、附錄 90
附錄A、The 17 antimicrobial agents and their standard zone diameter interpretive chart used in this study 90
附錄B、紙錠瓊脂擴散法(disc agar diffusion test) 91
附錄C、tetB Restriction Mapping 94
附錄D、tetD Restriction Mapping 95

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