第五章 實驗討論
5.5 其他未知型的 fusB insertion site 及基因結構
2009 年夫西地酸抗藥表皮葡萄球菌共有 4 株為 aj1-LP-fusB 未知型，1 株 aj1-LP-fusB 第一型，fusB 的 insertion site 皆為未知，分析其中 1 株 SeRIfusB-857序列
後，利用SeRIfusB-857已知序列設計核酸引子 (表八)，預測剩餘 4 株 insertion site 未
知之SeRIfusB是否位於 smpB 下游，分別設計引子黏接 RI 上游基因 smpB 與嵌和酶 int (upstream PCR)、嵌合酶基因 (integrase PCR)、 fusB 和下游基因(downstream PCR)和上游和下游基因 (chromosome PCR)，結果顯示 4 株 insertion site 未知之菌 株 (3 株 aj1-LP-fusB 未知型菌株和 1 株 aj1-LP-fusB 第一型菌株)，SeRIfusB可能都 位在 smpB 下游，且由 downstream PCR 都可以偵測到長片段的產物 (> 6kb)，推測 在其下游可能都帶有 transposase 和其帶的基因序列，但因無法預測其產物大小，
仍須進一步證明。而利用SeRIfusB-857 aj3 上基因序列設計引子，和 fusB 上黏接的引 子進行PCR 反應，aj1-LP-fusB 未知型菌株皆可以偵測到相同大小之 PCR 產物 (約 1.3K)，推測位在 smpB 下游的 aj1-LP-fusB 未知型菌株 SeRIfusB，可能 fusB 到 aj3
序列很相似。
5.6 脈衝式電泳分型
本篇利用脈衝式電泳分析夫西地酸抗藥菌株，在＞80％相似性的情形下，40 株菌株可以分成18 群集 (clusters)，顯示 2009 年夫西地酸抗藥表皮葡萄球菌並非 單一菌株傳播，而含有 fusB 的表皮葡萄球菌，雖然具有多種 pulsotyes，但大多可 發現SeRIfusB，SeRIfusB可能具有移動能力；金黃色葡萄球菌和表皮葡萄球菌具有一 些相同的嵌合酶，可以辨認相同的 attc site，暗示表皮葡萄球菌有可能會將夫西地 酸抗藥基因傳給金黃色葡萄球菌，雖然目前對於表皮葡萄球菌中SeRIfusB是否具有 移動能力還未知，但在金黃色葡萄球菌中PIs 具有移動能力曾被報導過(48)。
Type I
Type II
Type III
圖一、aj1-LP-fusB 結構 (11) 根據 aj1 片段大小可分成三種亞型 Type I：全長 aj1
Type II：aj1 93-421 個核苷酸 truncated，轉譯出較小的蛋白質 Type III：aj1 剩下游的 37 個核苷酸
aj1 LP fusB
LP fusB
△aj1
△aj1 LP fusB
圖二、南方墨點法偵測 fusB 限制酵素：HindIII；探針：fusB
M：digoxigenin-labeled DNA molecular weight marker II I-III：aj1-LP-fusB type I-III
U：aj1-LP-fusB undetermined type
Lane 1-10：NTUH526、857、3896、4893、6466、6844-2、9091、9080、2305、1848 Lane 11-20：NTUH 3525、7389、7667-1、8725、9232、9894、2745-2、5798-2、
6001、6547 (NTUH6001 為 fusA point mutation)
Lane 21-30：NTUH 7633、8357、1606、2692、1093、7230、2517、3553、6001-2、
7809
Lane 31-40：NTUH 1384、3869、4829-1、7686、7982、9481、103、2035、5025-2、
8055
2027 2322 4361 6557 9416 23130 bp
2027 2322 4361 6557 9416 23130 bp
M 1 2 3 4 5 6 7 8 9 10 M M 11 12 13 14 15 16 17 18 19 20 M
M 21 22 23 24 25 26 27 28 29 30 M M 31 32 33 34 35 36 37 38 39 40 M
II U III II III II II III II
II III II U II I II III II III I III III
圖三、2009 年夫西地酸抗藥表皮葡萄球菌基因分型 (genotypes)
夫西地酸抗藥表皮葡萄球菌 DNA，以 SmaI 限制酶切割後，利用 PFGE 分析其 pulsotypes， 用 BioNumerics 軟體以 UPGMA 演算法 (based on Dice similarity index)，在＞80％相似性的情形下，畫出樹狀圖，40 株菌株可以分成 18 群集
Dendrogram and pulsotype PFGE Isolates gene site
A B
圖四、Composite SeRI
fusB-857基因結構及其限制酶切位圖
Composite SeRIfusB-857基因結構主要可以分成兩個區域：(i) SeRIfusB-857 (S. epidermidis resistance island carrying fusB in NTUH857)：兩端為 15 bp 的 attc site，長度約為 15kb，總共包含
19 個 ORFs 和 1 個△ aj3。
(ii) SeCI857 (S. epidermidis chromosomal insertion in NTUH857)：transposase 後的基因序列，長度約為 5 kb，共有 8 個 ORFs。
下圖表示 Composite SeRIfusB-857限制酶切位 ( X：XbaI, S：SpeI, H：HindIII)
Composite SeRIfusB-857 (21.6 Kb)
圖五、Composite SeRI
fusB-857基因結構比較圖
27
S. epidermidis chromosome
27 smpB
S. epidermidis chromosome
SE0567 SE0568 SE0569 SE0570
(E)
(A) SeRI
fusB-704(GeneBank accession no. JF808725)
(B) Staphylococcus epidermidis 14.1.R1.SE ctg1131387704528 (GeneBank accession no. AGUC01000114) (C) Composite SeRI
fusB-857(D) Staphylococcus epidermidis FRI909
SePI 由 2 個 contings 組成：(i) conting 00004 (GeneBank accession no. AENR01000001) 和(ii) conting 00011 (GeneBank accession no. AENR01000008), 以 Sanger sequencing 確認兩段 conting 相接區域
(ORF8)。
(E) Staphylococcus epidermidis chromosome genes (Staphylococcus epidermidis ATCC12228)
抗藥性島嶼 (RI)嵌入 SsrA-binding protein (smpB)下游，Na
+-transporting ATP synthase 上游，原本位於 chromosome 上基因 SE0567- SE0570)會消失。smpB 位於 Staphylococcus epidermidis RP62A 的基因位 SERP0451 上。
灰色區域比較核苷酸間的相似程度，僅顯示相似程度大於 50％的區域，灰色區域的數字表示核苷酸相似程度百
分比。
箭頭表示預測的 open reading frames，預測產物詳述於表四：
Integrase and excisionase Virulence factor gene Chromosome gene Transcriptional regulator aj1-LP-fusB region
Primase Transposase
Terminase Hypothetical protein
Direct repeat (DR)以( )表示：
(A/C)GAGGCTGGGACATAATTCCTAGCAAAATAGCCAGTAAATGAGTTTTT(T/C)ATAAATTCATTTACTGGA TTATTT
attc
site 以( )表示：
SeRI
fusB-704位於 groEL 下游 (44’)，att
csite 為 ATGCCAGGTATGATGTAAAAA；SeRI
fusB-857、Staphylococcus
epidermidis 14.1.R1.SE 和 Staphylococcus epidermidis FRI909 位在 smpB 下游 (18’)，attc
site
TCCCGCCGTCTCCAT。
圖六、金黃色葡萄球菌基因序列
PI attc site 位置圖將金黃色葡萄球菌基因序列 (2.8Mb)以分鐘表示，圓圈外圍表示 60 分鐘，圓圈內圍表示 2.8 M 基因長度，正號或負號表示 PI insertion orientation 順時針或逆時針方向，SeRIfusB-857 insertion 在 18 分鐘的位置。
60’/0’ SeRIfusB-2793(-) SeRIfusB-704(-) SeRIfusB-5907(-) SsPI15305 (-)
表一、2009 年表皮葡萄球菌夫西地酸抗藥基因與 MIC 之關係
Resistantdeterminant
aj1-LP-fusB type
菌株 個數
不同MIC (μg/ml)菌株數目
2 4 8 16
Type I 2 0 0 2 0
fusB Type II 18 0 0 5 13
Type III 15 1 1 8 5
Undetermined 4 0 0 2 2
fusA - 1 0 0 0 1
總共 40 1 1 17 21
MIC：minimum inhibitory concentration
表二、2009 年表皮葡萄球菌 fusB insertion site
fusB insertionsite
aj1-LP-fusB type
Type I Type II Type III undetermined 總共
groEL 1 17 15 0 33
rpsR 0 1 0 0 1
undetermined 1 0 0 4 5
總共 2 18 15 4 39
.
表三、2009 年夫西地酸抗藥菌株 mecA 和 icaAB 分析
表四、ORFs of aj1-LP-fusB undetermined strain S. epidermidis NTUH857
Annotation Location(bp)
Size of encoded product (aa)
Predicted product Homologous protein [Sourse]
Accession No.
smpB ＜1-342 - SsrA-binding protein SsrA-binding protein
[Staphylococcus epidermidis ATCC12228]
NP_764121.1
1 903-1127 74 (complement)
Hypothetical protein Hypothetical protein SEVCU128_1987 [Staphylococcus epidermidis VCU128]
EHR95921.1
int 1139-2083 314
(complement)
Integrase Phage integrase family protein [Staphylococcus epidermidis FRI909]
EFV89353.1
2 2357-3007 216 (complement)
Transcriptional regulator Hypothetical protein HMPREF9981_07274 [Staphylococcus epidermidis NIHLM020]
EJE10045.1
3 3150-3368 72 Transcriptional regulator Conserved hypothetical protein
[Staphylococcus epidermidis BCM-HMP0060]
ZP_0482469 4.1
4 3532-3753 73 Hypothetical protein Conserved hypothetical protein [Staphylococcus warneri L37603]
ZP_0467823 7.1 5 3844-4110 88 Hypothetical protein Hypothetical protein
[Staphylococcus epidermidis VCU144]
EGG60387.1
6 4114-4425 108 Hypothetical protein Hypothetical protein HMPREF9983_11533 [Staphylococcus epidermidis NIHLM023]
EJE04513.1
7 4519-5391 290 Primase Pathogenicity island protein, partial [Staphylococcus epidermidis NIHLM053]
EJD99062.1
8 5404-6870 488 Virulence-associated protein E
Virulence-associated protein E [Staphylococcus epidermidis 14.1.R1.SE]
EHM70944.1
9 7160-7522 120 Pathogenicity island protein
Pathogenicity island protein
[Staphylococcus epidermidis NIHLM023]
EJE05098.1
10 7687-8448 253 Hypothetical protein Hypothetical protein SH2091 [Staphylococcus haemolyticus JCSC1435]
YP_254006.1
11 8796-9134 112 Pathogenicity island protein
Pathogenicity island family protein [Staphylococcus epidermidis NIHLM057]
EJD90718.1
12 9161-9844 227 Hypothetical protein Hypothetical protein HMPREF9989_12622 [Staphylococcus epidermidis NIHLM057]
EJD90719.1
13 9931-10389 152 Pathogenicity island protein
Pathogenicity island family protein [Staphylococcus epidermidis 14.1.R1.SE]
EHM70934.1
14 10392-10733 113 Hypothetical protein Hypothetical protein HMPREF9988_12898 [Staphylococcus epidermidis NIHLM053]
EJD90479.1
15 10738-11292 184 Terminase small subunit Phage terminase family protein [Staphylococcus epidermidis NIHLM049]
EJD95503.1
LP 12661-12723 20 fusB leader peptide SaRIfusB fusB leader peptide [Staphylococcus aureus CS6-EEFIC]
CAL23837.1
fusB 12799-13440 213 FusB SaRIfusB fusB
[Staphylococcus aureus CS6-EEFIC]
AAN07146.1
aj2 13705-14163 152 aj2 S. aureus pUB101 NP_932196
ᇞaj3 14330-14795 - △aj3 S. aureus pUB101 NP_932195
tnp 15831-16844 337 Transposase ISSep1-like transposase [Staphylococcus aureus]
BAG84190.1
16 17075-17188 37 (complement)
Hypothetical protein Hypothetical protein GSEF_0159 [Staphylococcus epidermidis FRI909]
EFV90062.1
17 17680-17988 102 Hypothetical protein Conserved hypothetical protein [Staphylococcus epidermidis FRI909]
EFV90061.1
18 18034-18294 86 Terminase small subunit Conserved hypothetical protein [Staphylococcus epidermidis FRI909]
EFV90060.1
19 18548-18790 88 (complement)
Hypothetical protein Conserved hypothetical protein [Staphylococcus epidermidis W23144]
ZP_0479660 2.1 20 19200-20522 440 Hypothetical protein Hypothetical protein SEVCU071_0911
[Staphylococcus epidermidis VCU071]
EHM66636.1
21 20534-20833 99 Hypothetical protein Hypothetical protein HMPREF9989_10436 [Staphylococcus epidermidis NIHLM057]
EJD91439.1
22 21051-21476 141 (complement)
Hypothetical protein Hypothetical protein GSEF_0151 [Staphylococcus epidermidis FRI909]
EFV90054.1
23 21515-21775 86 Hypothetical protein Hypothetical protein HMPREF9956_0569 [Staphylococcus epidermidis 14.1.R1.SE]
EHM73971.1
24 21970-＞22080 - Na+-transporting ATP synthase
Na+-transporting ATP synthase [Staphylococcus epidermidis ATCC12228]
NP_764126.1
表五、2008~2009 年表皮葡萄球菌 夫西地酸抗藥基因與 MIC 之關係 Resistant
determinant
aj1-LP-fusB type
2008-2009 菌株個數
不同MIC (μg/ml)菌株數目
2 4 8 16 32
Type I 7 0 1 3 3 0
fusB Type II 41 0 0 8 33 0
Type III 39 1 11 16 11 0
Undetermined 15 0 1 8 6 0
fusC - 2 0 0 0 1 1
fusA - 1 0 0 0 1 0
總共 105 1 13 35 55 1
表六、2008~2009 年表皮葡萄球菌抗藥基因整理
抗藥基因 基因型 菌株數目 (百分比)
2008 年 2009 年 fus fene
fusB 63 (97％) 39 (97.5％)
fusC 2 (3％) 0 (0％)
fusA mutation 0 (0％) 1 (2.5％)
aj1-LP-fusB type
Type I 5 (7.9％) 2 (5.1％) Type II 23 (36.5％) 18 (46.1％) Type III 24 (38％) 15 (38.5％) undetermined 11 (17.5％) 4 (10.3％)
fusB insertion site
groEL 50 (79.4％) 33 (84.6％)
rpsR 0 (0％) 1 (2.6％)
undetermined 13 (20.6％) 5 (12.8％) 2008 年菌株資料來源(54)
表七、2009 年表皮葡萄球菌臨床菌株
NO. 菌株編號 檢體來源 fus gene FA MIC mecA icaAB CC E GEM OX SXT 1 NTUH526 血液 B 16 + + R R R R R
2 NTUH857 血液 B 8 + - S R R R R
3 NTUH3896 血液 B 16 + + S S R R R
4 NTUH4893 血液 B 8 + + R R R R R
5 NTUH6466 血液 B 16 + + R R R R R
6 NTUH6844-2 血液 B 16 + + R R R R R 7 NTUH9091 血液 B 16 + + R R R R R
8 NTUH9080 血液 B 16 + + R R R R R
9 NTUH2305 血液 B 16 + + S S R R R
10 NTUH1848 血液 B 16 + + R R R R R
11 NTUH3525 血液 B 8 + + S S R R R
12 NTUH7389 血液 B 16 + + R R R R R
13 NTUH7667-1 血液 B 16 + + R R R R R
14 NTUH8725 血液 B 16 + － S S S R S
15 NTUH9232 血液 B 2 + + R R R R R
16 NTUH9894 血液 B 16 + + R R R R S
17 NTUH2745-2 血液 B 8 + + S I R R R
18 NTUH5798-2 血液 B 8 + + S S R R R
19 NTUH6001 血液 A 16 + － S R R R S
20 NTUH6547 血液 B 16 + + R R R R R
21 NTUH7633 血液 B 16 + + S S R R S
22 NTUH8357 血液 B 16 + + R R R R R
23 NTUH1606 血液 B 16 + + R R R R R
24 NTUH2692 血液 B 8 + + R R R R R
25 NTUH1093 腦脊髓液 B 8 + + R R R R R
26 NTUH7230 血液 B 16 + + R R R R R
27 NTUH2517 血液 B 16 + － R R S R R
28 NTUH3553 血液 B 16 + － S R R R R
29 NTUH6001-2 血液 B 8 + + R R R R R
30 NTUH7809 血液 B 8 + + R R R R R
31 NTUH1384 血液 B 8 + － S R R R R
32 NTUH3869 血液 B 8 + + R R R R R
33 NTUH4829-1 血液 B 8 + + R R R R S
34 NTUH7686 血液 B 8 + + R R R R R
35 NTUH7982 血液 B 8 + + R R R R R
36 NTUH9481 血液 B 8 + + R R R R R
37 NTUH103 血液 B 16 + + R R R R R
38 NTUH2035 血液 B 8 + + R R R R R
39 NTUH5025-2 血液 B 8 + － S S S R R
40 NTUH8055 血液 B 4 + + R R R R R
FA：fusidic acid, CC：clindamycin, E：erythromycin, GEM：gemtamycin, OX：oxicillin, SXT：trimethoprim/sulfamethoxazole CC, E, GEM, OX, SXT 抗生素資料來自台大醫院細菌室
表八、核酸引子列表
Description Primer name Sequence (5’to 3’)
Specific
and fusB specific probe S.epi groEL1582-1599F GAA CAA CCT GGA ATG GGT
185LA3R CTC ACA GAG GTT CTA TAA TGT TGG S.epi sodium transpoter140-162 (R) TCT CAC TAT GGA TTT AAC TTC CG S.epi ssrA-binding protein (F) AAG ATA CAA TTG AAG CGG GG
mecA detection mecA 375-392F AGA TTG GGA TCA TAG CGT
mecA-1091 GGT GTG CTT ACA AGT GCT AA
icaAB detection icaAB-F TTA TCA ATG CCG CAG TTG TC
icaAB-R GTT TAA CGC GAG TGC GCT AT
LA PCR fusB 531-559F CGG ATG GTC AAT ATG TAA AAA AAG GTG AC
fusB 437-467F GAG AAA TTT CTA ATC AGG TTG TAA AGG GG fusB 389-361R TTC CGA TTT GAT GCA AGT TCA TTC CAT CC fusB 282-253R AAG TTT TTG CGG ACT AGG TAG TTC AAA AGG fusB 554-581F GGT GAC TAT ATA TGT CGA GAT AGC ATT C fusB 222-193R GCT TCA ATT TCT TTG TTT GAT AAT CTG ATG Sequence of fusB
and flanking region
s.epi 2821-2841(F) GGG CTT TTT GTT TTT GGG TGC s.epi speI up 33-65(F) TTG AGC CCT GAA TAT TAA TAG GG s.epi speI down 191-212(R) GAC TAC AGA CTG AAG CTT GCC C S. epi inverse 21-1(R) GTT TCA CTC ATC GCA ACA CAG S. epi inverse 1990-2007(F) AGG TGC GAA GAT TGC AGG
S. epi 857aj3 218-242(R) CAT TTT CCT CAA CAT ATA GAA GTT C s.epi HindIII-2(R) TAT TAA ATG CAA CAG GCA ACC S.epi Hind-3(F) TCG TTA ACT TTA TCC ACC CG S.epi sodium transpoter 52-71 (R) ATT AGT AGA GCG CTT GTT CC S.epi PacI-4(R) GAC GCA TCT CTG TTA TGA CG
s.epi down 35(R) CCC TAC AGA CCC TCC TTG TG s.epi down 36(F) GTC TTA TAA CAA TTT GAA AAG GG s.epi down 37(F) AGC AAA GTC TAC CCA TCA GC S.epi down 40(F) AAA AAA CTC CAA TGG GAA GC Primer sequence used in this study. M：A＋C
參考文獻
1. A. Wali Karzai, Miriam M. Susskind, and Robert T. Sauer. 1999. SmpB, a unique RNA-binding protein essential for the peptide-tagging activity of SsrA (tmRNA). EMBO J 18:3793-3799.
2. Agirrezabala, X., and J. Frank. 2009. Elongation in translation as a dynamic interaction among the ribosome, tRNA, and elongation factors EF-G and EF-Tu.
Q Rev Biophys 42:159-200.
3. Archer, G.L., and J.L. Johnston. 1983. Self-transmissible plasmids in Staphylococci that encode resistance to aminoglycosides. Antimicrob. Agents Chemother. 24:70-77.
4. Baba, T., F. Takeuchi, M. Kuroda, H. Yuzawa, K.-i. Aoki, A. Oguchi, Y.
Nagai, N. Iwama, K. Asano, T. Naimi, H. Kuroda, L. Cui, K. Yamamoto, and K. Hiramatsu. 2002. Genome and virulence determinants of high virulence community-acquired MRSA. The Lancet 359:1819-1827.
5. Ban, N., P. Nissen, J. Hansen, P.B. Moore, and T.A. Steitz. 2000. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution.
Science 289:905-920.
6. Besier, S., A. Ludwig, V. Brade, and T.A. Wichelhaus. 2003. Molecular analysis of fusidic acid resistance in Staphylococcus aureus. Mol. Microbiol.
47:463-469.
7. Brian F. Cheetham, David B. Tattersall, Garry A. Bloomfield, Julian I.
Rood, and Margaret E. Katz. 1995. Identification of a gene encoding a bacteriophage-related integrase in a vap region of the Dichelobacter nodosus genome Gene 162:53-58.
8. Castanheira, M., A.A. Watters, J.M. Bell, J.D. Turnidge, and R.N. Jones.
2010. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008.
Antimicrob. Agents Chemother. 54:3614-3617.
9. Chen, C.M., M. Huang, H.F. Chen, S.C. Ke, C.R. Li, J.H. Wang, and L.-T.
Wu. 2011. Fusidic acid resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in a Taiwanese hospital. BMC Microbiology 11:98-106.
10. Chen, H.J., W.C. Hung, S.P. Tseng, J.C. Tsai, P.R. Hsueh, and L.J. Teng.
2010. Fusidic acid resistance determinants in Staphylococcus aureus clinical isolates. Antimicrob. Agents Chemother. 54:4985-4991.
11. Chen, H.J., J.C. Tsai, W.C. Hung, S.P. Tseng, P.R. Hsueh, and L.J. Teng.
2011. Identification of fusB-mediated fusidic acid resistance islands in Staphylococcus epidermidis isolates. Antimicrob. Agents Chemother.
55:5842-5849.
12. Chen, Y., R.K. Koripella, S. Sanyal, and M. Selmer. 2010. Staphylococcus aureus elongation factor G-structure and analysis of a target for fusidic acid. The FEBS journal 277:3789-3803.
13. Dobie, D., and J. Gray. 2004. Fusidic acid resistance in Staphylococcus aureus.
Arch. Dis. Child. 89:74-77.
14. Frebourg, N.B., S. Lefebvre, S. Baert, and J.F. Lemeland. 2000. PCR-based assay for discrimination between invasive and contaminating Staphylococcus epidermidis strains. J. Clin. Microbiol. 38:877–880.
15. Garry A. Bloomfield, Gabrielle Whittle, Matthew B. McDonagh, Margaret E. Katz, and Brian F. Cheetharn. 1997. Analysis of sequences flanking the vap regions of Dichelobacter nodosus: evidence for multiple integration events, a killer system, and a new genetic element. Microbiology 143:553-562.
16. Graves, S.F., S.D. Kobayashi, and F.R. DeLeo. 2010. Community-associated methicillin-resistant Staphylococcus aureus immune evasion and virulence. J Mol Med (Berl) 88:109-114.
17. Hacker, J., and J.B. Kaper. 2000. Pathogenicity islands and the evolution of microbes. Annu. Rev. Microbiol. 54:641-679.
18. Hauschild, T., and S. Stepanovic´. 2008. Identification of Staphylococcus spp.
by PCR-restriction fragment length polymorphism analysis of dnaJ gene. J. Clin.
Microbiol. 46:3875-3879.
19. Heilmann, C., O. Schweitzer, C. Gerke, N. Vanittanakom, D. Mack, and F.
Gotz. 1996. Molecular basis of intercellular adhesion in the biofilm-fornimg Staphylococcus epidermidis. Mol. Microbiol. 20:1083-1091.
20. Howden, B.P., and M.L. Grayson. 2006. Dumb and dumber—the potential waste of a useful antistaphylococcal agent: emerging fusidic acid resistance in Staphylococcus aureus. Clin. Infect. Dis. 42:394-400.
21. James P. O'Gara JP, and Hilary Humphreys H. 2001. Staphylococcus epidermidis biofilms: importance and implications. J Med Microbiol 50:582-587.
22. Jodi A. Lindsay, Alexey Ruzin, Hope F. Ross, natasha Kurepina, and Richard P. Novick. 1998. The gene for toxic shock toxin is carried by a family of mobile pathogenicity islands in S. aureus. Mol Microbiol 29:527-543.
23. Kuroda, M., T. Ohta, I. Uchiyama, T. Baba, H. Yuzawa, I. Kobayashi, L.
Cui, A. Oguchi, K.-i. Aoki, Y. Nagai, J. Lian, T. Ito, M. Kanamori, H.
Matsumaru, A. Maruyama, H. Murakami, A. Hosoyama, Y. Mizutani Ui, N.K. Takahashi, T. Sawano, R.i. Inoue, C. Kaito, K. Sekimizu, H. Hirakawa, S. Kuhara, S. Goto, J. Yabuzaki, M. Kanehisa, A. Yamashita, K. Oshima, K.
Furuya, C. Yoshino, T. Shiba, M. Hattori, N. Ogasawara, H. Hayashi, and K.
Hiramatsu. 2001. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357:1225-1240.
24. Langille, M.G., W.W. Hsiao, and F.S. Brinkman. 2010. Detecting genomic islands using bioinformatics approaches. Nat. Rev. Microbiol. 8:373-382.
25. Laurberg, M., O. Kristensen, K. Martemyanov, A.T. Gudkov, I. Nagaev, D.
Hughes, and A. Liljas. 2000. Structure of a mutant EF-G reveals domain III and possibly the fusidic acid binding site. J. Mol Biol 603:593-603.
26. Lindsay, J.A., A. Ruzin, H.F. Ross, N. Kurepina, and R.P. Novick. 1998. The gene for toxic shock shock toxin is carried by a family of mobile pathogenecity islands is Staphylococcus aureus. Mol. Microbiol. 29:527-543.
27. Liu, D., E. Swiatlo, F.W. Austin, and M.L. Lawrence. 2006. Use of a putative transcriptional regulator gene as target for specific identification of Staphylococcus epidermidis. Lett Appl Microbiol 43:325-330.
28. Madhusoodanan, J., K.S. Seo, B. Remortel, J.Y. Park, S.Y. Hwang, L.K.
Fox, Y.H. Park, C.F. Deobald, D. Wang, S. Liu, S.C. Daugherty, A.L. Gill, G.A. Bohach, and S.R. Gill. 2011. An enterotoxin-bearing pathogenicity island in Staphylococcus epidermidis. J. Bacteriol. 193:1854-1862.
29. Margaret E. katz, Pauline M. Howarth, Weng K. Yong, George G. Riffkin, Laurie J. Depiazzi, and Julian I. Rood. 1991. Identification of three gene regions associated with virulence in Dichelobacter nodosus, the causative agent of ovine footrot. J. Gen. Microbiol. 137:2117-2124.
30. McLaws, F., I. Chopra, and A.J. O' Neill. 2008. High prevalence of resistance to fusidic acid in clinical isolates of Staphylococcus epidermidis. J. Antimicrob.
Chemother. 61:1040-1043.
31. Mempel, M., H. Feucht, W. Ziebuhr, M. Endres, R. Laufs, and L. Gruter.
1994. Lack of mecA transcription in slime-negative phase variantsof methicillin-resistant Staphylococcus epidermidis. Antimicrob. Agents Chemother.
38:1251-1255.
32. Nagaev, I., J. Björkman, D.I. Andersson, and D. Hughes. 2001. Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus.
Mol. Microbiol. 40:433-439.
33. Norstrom, T., J. Lannergard, and D. Hughes. 2007. Genetic and phenotypic identification of fusidic acid-resistant mutants with the small-colony-variant phenotype in Staphylococcus aureus. Antimicrob. Agents Chemother.
51:4438-4446.
34. Novick, R.P., G.E. Christie, and J.R. Penades. 2010. The phage-related chromosomal islands of Gram-positive bacteria. Nat. Rev. Microbiol. 8:541-551.
35. Novick, R.P., and A. Subedi. 2007. The SaPIs mobile pathogenicity islands of
Staphylococcus. Chem Immunol Allergy 93:42-57.
36. O' Brien, F.G., C. Price, W.B. Grubb, and J.E. Gustafson. 2002. Genetic characterization of the fusidic acid and cadmium resistance determinants of Staphylococcus aureus plasmid pUB101. J. Antimicrob. Chemother. 50:313-321.
37. O' Neill, A.J., and I. Chopra. 2006. Molecular basis of fusB-mediated resistance to fusidic acid in Staphylococcus aureus. Mol. Microbiol. 59:664-676.
38. O'Neill, A.J., A.R. Larsen, R. Skov, Henriksen, A. S. , and I. Chopra. 2007.
Characterization of the epidemic european fusidic acid-resistant impetigo clone of Staphylococcus aureus. J Clin Microbiol 45:1505-1510.
39. O'Neill, A.J., F. McLaws, G. Kahlmeter, A.S. Henriksen, and I. Chopra.
2007. Genetic basis of resistance to fusidic acid in Staphylococci. Antimicrob.
Agents Chemother. 51:1737-1740.
40. O"Neill, A.J., A.R. Larsen, A.S. Henriksen, and I. Chopra. 2004. A fusidic acid-resistant epidemic strain of Staphylococcus aureus carries the fusB determinant, whereas fusA Mutations are prevalent in other resistant isolates.
Antimicrob. Agents Chemother. 48:3594-3597.
41. Otto, M. 2009. Staphylococcus epidermidis — the 'accidental' pathogen. Naturre Reviews Microbiology 7:555-567.
42. P, C., and T. J. 1999. Fusidic acid in vitro activity. Int J Antimicrob Agents 12(suppl 2):S45-58.
43. Ramrath, D.J., H. Yamamoto, K. Rother, D. Wittek, M. Pech, T. Mielke, J.
Loerke, P. Scheerer, P. Ivanov, Y. Teraoka, O. Shpanchenko, K.H. Nierhaus, and C.M. Spahn. 2012. The complex of tmRNA-SmpB and EF-G on translocating ribosomes. nature 485:526-529.
44. Shah, M.M., H. Iihara, M. Noda, S.X. Song, P.H. Nhung, K. Ohkusu, Y.
Kawamura, and T. Ezaki. 2007. dnaJ gene sequence-based assay for species identification and phylogenetic grouping in the genus Staphylococcus. Int J Syst Evol Micr 57:25-30.
45. Skold, S.E. 1982. Chemical cross-linking of elongation factor G to both subunits of the 70-S ribosomes from Escherichia coli. Eur J Biochem 127:225-229.
46. Subedi, A., C. Ubeda, R.P. Adhikari, J.R. Penadés, and R.P. Novick. 2007.
Sequence analysis reveals genetic exchanges and intraspecific spread of SaPI2, a pathogenicity island involved in menstrual toxic shock. Microbiology 158:3235-3245.
47. Takahashi, T., l. Satoh, and N. Kikuchi. 1999. Phylogenetic relationships of 38 taxa of the genus Staphylococcus based on 16S rRNA gene sequence analysis.
Int J Syst Bacteriol 49:725-728.
48. Tormo-Mas, M.A., I. Mir, A. Shrestha, S.M. Tallent, S. Campoy, I. Lasa, J.
Barbe, R.P. Novick, G.E. Christie, and J.R. Penades. 2010. Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Nature 465:779-782.
49. Turlan, C., and M. Chandler. 1995. IS1-mediated intramolecular rearrangments: formation of excised transposon circles and replication deletions.
EMBO J 14:5410-5421.
50. Ubeda, C., E. Maiques, E. Knecht, I. Lasa, R.P. Novick, and J.R. Penades.
2005. Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Mol. Microbiol.
56:836-844.
51. Vuong, C., and M. Otto. 2002. Staphylococcus epidermidis infections.
Microbes Infect 4:481-489.
52. Worthington, T., P.A. Lambert, and T.S. Elliott. 2000. Is hospital-acquired intravascular catheter-related sepsis associated with outbreak strains of coagulase-negative staphylococci? J Hosp Infect 46:130-134.
53. Zinn, C.S., H. Westh, and V.T. Rosdahl. 2004. An international multicenter study of antimicrobial resistance and typing of hospital staphylococcus aureus isolates from 21 laboratories in 19 countries or states. Microb Drug Resist 10:160-168.
54. 游尚捷。2011。表皮葡萄球菌對夫西地酸之抗藥基因及亞型分析。國立臺灣 大學碩士論文