第五章 結論與建議
第二節 建議
我們發現 B. henselae 感染細胞後,會經由抑制粒線體內在凋亡路徑,
然而 B. henselae 所引發的訊息傳遞路徑,可能不僅有 Bad、Bcl-xL、
cytochrome c、caspase 9 及 caspase 3 這條路徑,為能更了解完整的細胞反 應,可觀察其他與細菌感染相關的訊息傳遞路徑,如 interferon α及 tumour necrosis factor α [53]。而於蛋白質體研究方面,為了能持續研究於 實驗中所發現之特異性的蛋白質分子,如: small heat shock protein、
acetyl-CoA carboxylase carboxyltransferase subunit alpha、phage related protein 及 superoxide dismutase [Cu-Zn] precursor,可使用 gene knockout 的方式,研究 B. henselae 在缺乏這些蛋白質的情況下,其感染細胞的能 力是否會改變,確立這些蛋白質的影響,對於 B. henselae 致病機轉的研 究就能有更大的突破。
參考文獻
1. Chomel, B.B., et al., Experimental transmission of Bartonella henselae by the cat flea. J Clin Microbiol, 1996. 34(8): p. 1952-6.
2. Bass, J.W., J.M. Vincent, and D.A. Person, The expanding spectrum of Bartonella infections: II. Cat-scratch disease. Pediatr Infect Dis J, 1997.
16(2): p. 163-79.
3. Holmes, A.H., et al., Bartonella henselae endocarditis in an immunocompetent adult. Clin Infect Dis, 1995. 21(4): p. 1004-7.
4. Koehler, J.E., et al., Molecular epidemiology of bartonella infections in patients with bacillary angiomatosis-peliosis. N Engl J Med, 1997.
337(26): p. 1876-83.
5. Reed, J.A., et al., Immunocytochemical identification of Rochalimaea henselae in bacillary (epithelioid) angiomatosis, parenchymal bacillary peliosis, and persistent fever with bacteremia. Am J Surg Pathol, 1992.
16(7): p. 650-7.
6. Shenep, J.L., Cat-scratch disease and Bartonella henselae infections in children. Pediatr Ann, 1996. 25(9): p. 518-23.
7. Kostianovsky, M. and M.A. Greco, Angiogenic process in bacillary angiomatosis. Ultrastruct Pathol, 1994. 18(3): p. 349-55.
8. Dehio, C., Recent progress in understanding Bartonella-induced vascular proliferation. Curr Opin Microbiol, 2003. 6(1): p. 61-5.
9. Fuhrmann, O., et al., Bartonella henselae induces NF-kappaB-dependent upregulation of adhesion molecules in cultured human endothelial cells: possible role of outer membrane proteins as pathogenic factors. Infect Immun, 2001. 69(8): p. 5088-97.
10. Schmid, M.C., et al., The VirB type IV secretion system of Bartonella henselae mediates invasion, proinflammatory activation and antiapoptotic protection of endothelial cells. Mol Microbiol, 2004.
52(1): p. 81-92.
11. Kirby, J.E. and D.M. Nekorchuk, Bartonella-associated endothelial proliferation depends on inhibition of apoptosis. Proc Natl Acad Sci U S A, 2002. 99(7): p. 4656-61.
12. Dehio, C., Molecular and cellular basis of bartonella pathogenesis.
Annu Rev Microbiol, 2004. 58: p. 365-90.
13. Slater, L.N., et al., A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia. N Engl J Med, 1990.
323(23): p. 1587-93.
14. Regnery, R.L., et al., Characterization of a novel Rochalimaea species, R. henselae sp. nov., isolated from blood of a febrile, human immunodeficiency virus-positive patient. J Clin Microbiol, 1992. 30(2):
p. 265-74.
15. Brenner, D.J., et al., Proposals to unify the genera Bartonella and Rochalimaea, with descriptions of Bartonella quintana comb. nov., Bartonella vinsonii comb. nov., Bartonella henselae comb. nov., and Bartonella elizabethae comb. nov., and to remove the family Bartonellaceae from the order Rickettsiales. Int J Syst Bacteriol, 1993.
43(4): p. 777-86.
16. Alsmark, C.M., et al., The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae. Proc Natl Acad Sci U S A, 2004. 101(26): p. 9716-21.
17. Bergmans, A.M., et al., Predominance of two Bartonella henselae variants among cat-scratch disease patients in the Netherlands. J Clin Microbiol, 1996. 34(2): p. 254-60.
18. Woestyn, S., et al., Study of genotypes and virB4 secretion gene of Bartonella henselae strains from patients with clinically defined cat scratch disease. J Clin Microbiol, 2004. 42(4): p. 1420-7.
19. Yamamoto, K., et al., Infection and re-infection of domestic cats with various Bartonella species or types: B. henselae type I is protective against heterologous challenge with B. henselae type II. Vet Microbiol, 2003. 92(1-2): p. 73-86.
20. Yamamoto, K., et al., Homologous protection but lack of heterologous-protection by various species and types of Bartonella in specific pathogen-free cats. Vet Immunol Immunopathol, 1998. 65(2-4):
p. 191-204.
21. Sander, A., et al., Comparison of different DNA fingerprinting techniques for molecular typing of Bartonella henselae isolates. J Clin Microbiol, 1998. 36(10): p. 2973-81.
22. Sander, A., et al., Detection of Bartonella henselae DNA by two different PCR assays and determination of the genotypes of strains involved in histologically defined cat scratch disease. J Clin Microbiol, 1999. 37(4): p. 993-7.
23. Chang, C.C., et al., Molecular epidemiology of Bartonella henselae infection in human immunodeficiency virus-infected patients and their cat contacts, using pulsed-field gel electrophoresis and genotyping. J Infect Dis, 2002. 186(12): p. 1733-9.
24. Dillon, B., et al., Limited diversity among human isolates of Bartonella henselae. J Clin Microbiol, 2002. 40(12): p. 4691-9.
25. Drancourt, M. and D. Raoult, Proposed tests for the routine identification of Rochalimaea species. Eur J Clin Microbiol Infect Dis, 1993. 12(9): p. 710-3.
26. Kordick, D.L. and E.B. Breitschwerdt, Intraerythrocytic presence of Bartonella henselae. J Clin Microbiol, 1995. 33(6): p. 1655-6.
27. Arlet, G. and Y. Perol-Vauchez, The current status of cat-scratch disease: an update. Comp Immunol Microbiol Infect Dis, 1991. 14(3):
p. 223-8.
28. Chomel, B.B., Cat-scratch disease. Rev Sci Tech, 2000. 19(1): p.
136-50.
29. Schulein, R., et al., Invasion and persistent intracellular colonization of erythrocytes. A unique parasitic strategy of the emerging pathogen Bartonella. J Exp Med, 2001. 193(9): p. 1077-86.
30. Dehio, C., Bartonella-host-cell interactions and vascular tumour formation. Nat Rev Microbiol, 2005. 3(8): p. 621-31.
31. Chomel, B.B., et al., Ecological fitness and strategies of adaptation of Bartonella species to their hosts and vectors. Vet Res, 2009. 40(2): p.
29.
32. Boulouis, H.J., et al., Factors associated with the rapid emergence of zoonotic Bartonella infections. Vet Res, 2005. 36(3): p. 383-410.
33. Chang, C.C., et al., Cat-scratch disease in veterinary-associated populations and in its cat reservoir in Taiwan. Vet Res, 2006. 37(4): p.
565-77.
34. Lee, S.C., et al., Cat-scratch disease caused by Bartonella henselae:
the first case report in Taiwan. J Formos Med Assoc, 1998. 97(8): p.
569-72.
35. Kumasaka, K., et al., Survey of veterinary professionals for antibodies to Bartonella henselae in Japan. Rinsho Byori, 2001. 49(9): p. 906-10.
36. Maruyama, S., et al., Prevalence of Bartonella species and 16s rRNA gene types of Bartonella henselae from domestic cats in Thailand. Am J Trop Med Hyg, 2001. 65(6): p. 783-7.
37. Schulein, R. and C. Dehio, The VirB/VirD4 type IV secretion system of Bartonella is essential for establishing intraerythrocytic infection. Mol Microbiol, 2002. 46(4): p. 1053-67.
38. Schulein, R., et al., A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells. Proc Natl
Acad Sci U S A, 2005. 102(3): p. 856-61.
39. Zhang, P., et al., A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella quintana. Proc Natl Acad Sci U S A, 2004. 101(37): p. 13630-5.
40. Riess, T., et al., Bartonella adhesin a mediates a proangiogenic host cell response. J Exp Med, 2004. 200(10): p. 1267-78.
41. Kempf, V.A., et al., Do plant and human pathogens have a common pathogenicity strategy? Trends Microbiol, 2002. 10(6): p. 269-75.
42. Schmiederer, M., et al., Intracellular induction of the Bartonella henselae virB operon by human endothelial cells. Infect Immun, 2001.
69(10): p. 6495-502.
43. Pulliainen, A.T. and C. Dehio, Bartonella henselae: subversion of vascular endothelial cell functions by translocated bacterial effector proteins. Int J Biochem Cell Biol, 2009. 41(3): p. 507-10.
44. Minnick, M.F. and B.E. Anderson, Bartonella interactions with host cells. Subcell Biochem, 2000. 33: p. 97-123.
45. Kempf, V.A., et al., Activation of hypoxia-inducible factor-1 in bacillary angiomatosis: evidence for a role of hypoxia-inducible factor-1 in bacterial infections. Circulation, 2005. 111(8): p. 1054-62.
46. Kempf, V.A., et al., Evidence of a leading role for VEGF in Bartonella henselae-induced endothelial cell proliferations. Cell Microbiol, 2001.
3(9): p. 623-32.
47. Dehio, C., et al., Interaction of Bartonella henselae with endothelial cells results in bacterial aggregation on the cell surface and the subsequent engulfment and internalisation of the bacterial aggregate by a unique structure, the invasome. J Cell Sci, 1997. 110 ( Pt 18): p.
2141-54.
48. Manders, S.M., Bacillary angiomatosis. Clin Dermatol, 1996. 14(3): p.
295-9.
49. McCord, A.M., S.I. Resto-Ruiz, and B.E. Anderson, Autocrine role for interleukin-8 in Bartonella henselae-induced angiogenesis. Infect Immun, 2006. 74(9): p. 5185-90.
50. De Martin, R., et al., The transcription factor NF-kappa B and the regulation of vascular cell function. Arterioscler Thromb Vasc Biol, 2000. 20(11): p. E83-8.
51. Nicholson, D.W., Apoptosis. Baiting death inhibitors. Nature, 2001.
410(6824): p. 33-4.
52. Schmid, M.C., et al., A translocated bacterial protein protects vascular
endothelial cells from apoptosis. PLoS Pathog, 2006. 2(11): p. e115.
53. Dehio, M., et al., The transcriptional response of human endothelial cells to infection with Bartonella henselae is dominated by genes controlling innate immune responses, cell cycle, and vascular remodelling. Thromb Haemost, 2005. 94(2): p. 347-61.
54. Kempf, V.A., et al., Bartonella henselae inhibits apoptosis in Mono Mac 6 cells. Cell Microbiol, 2005. 7(1): p. 91-104.
55. Martin, M.C., et al., Protein kinase A regulates caspase-9 activation by Apaf-1 downstream of cytochrome c. J Biol Chem, 2005. 280(15): p.
15449-55.
56. Kuczynska-Wisnik, D., et al., Escherichia coli small heat shock proteins IbpA/B enhance activity of enzymes sequestered in inclusion bodies. Acta Biochim Pol, 2004. 51(4): p. 925-31.
57. Lai, E.M., et al., Proteomic analysis of Agrobacterium tumefaciens response to the Vir gene inducer acetosyringone. Proteomics, 2006.
6(14): p. 4130-6.
58. Matuszewska, E., et al., Escherichia coli heat-shock proteins IbpA/B are involved in resistance to oxidative stress induced by copper.
Microbiology, 2008. 154(Pt 6): p. 1739-47.
59. Liu, X., P.D. Fortin, and C.T. Walsh, Andrimid producers encode an acetyl-CoA carboxyltransferase subunit resistant to the action of the antibiotic. Proc Natl Acad Sci U S A, 2008. 105(36): p. 13321-6.
60. Zhang, R. and C.T. Zhang, Identification of genomic islands in the genome of Bacillus cereus by comparative analysis with Bacillus anthracis. Physiol Genomics, 2003. 16(1): p. 19-23.
61. Craig, M. and J.M. Slauch, Phagocytic superoxide specifically damages an extracytoplasmic target to inhibit or kill Salmonella. PLoS ONE, 2009. 4(3): p. e4975.
62. Huang, Z.G., et al., Mutation of cytotoxin-associated gene A affects expressions of antioxidant proteins of Helicobacter pylori. World J Gastroenterol, 2009. 15(5): p. 599-606.
附錄一、各分離株中 4 個可能毒力因子之基因庫序號
Protein Strain Genebank
Accession No.
BU4 GQ220306
JK40 GQ220307 Small heat shock protein
JK47 GQ220308
BU4 GQ227672
JK40 GQ227674 Acetyl-CoA carboxylase
carboxyltransferase subunit
alpha JK47 GQ227673
BU4 GQ227675
JK40 GQ227677 Phage related protein
JK47 GQ227676
BU4 GQ227678
JK40 GQ227680 Superoxide dismutase
[Cu-Zn ] precursor
JK47 GQ227679
附錄二、B. henselae 分離株中 4 個可能毒力因子之核酸及胺基酸序列比 對,取差異較大片段陳列。
(A) Small heat shock protein 核酸序列比對
(B) Acetyl-CoA carboxylase carboxyltransferase subunit alpha 核酸序列比對
(C) Phage related protein 核酸序列比對
(D) Superoxide dismutase [Cu-Zn ] precursor 核酸序列比對
(A) Small heat shock protein 胺基酸序列比對
(B) Acetyl-CoA carboxylase carboxyltransferase subunit alpha 胺基酸序列比 對
(C) Phage related protein 胺基酸序列比對
(D) Superoxide dismutase [Cu-Zn ] precursor 胺基酸序列比對
附錄三、實驗數據總表 Proliferation (cell number)
Inhibition of Apoptosis (cell number) Strain
24hr 48hr 72hr 24hr 48hr 72hr
MOI50
Control 19250±1650 20166.7±1587.7 36666.7±4200.7 13016.7±2222.8 12283.3±840.1 10450±550 Hous 17556±653.4 26888.9±2240.7 35357.1±1964.3 13646.5±4727.3 14575±275 10266.7±840.1 U-4 19983.3±2289.8 17839.7±1343.4 45000±2500 10633.3±635.1 13639.3±239.3 13999.1±1231.3 JK47 19140±1438.4 18043.9±1838.4 44000±7275.8 10413.3±0 12706.9±1270.7 11064.7±0 JK40 21526.9±358.5 21083.3±1587.7 63931.6±4308.4 10413.3±0 10364.1±1994.6 15675±1741.7 MOI100
Control 19250±1650 20166.7±1587.7 36666.7±4200.7 13016.7±2222.8 12283.3±840.1 10450±550 Hous 16632±462 26142.0±3422.8 36666.7±3000.5 13226.6±3562.9 17600±550 9350±550 U-4 19800±2520.4 17839.7±1343.4 54166.7±5204.2 13200±1455.2 13639.3±239.3 16365.1±683 JK47 18260±381.1 19105.3±0 32083.3±1587.7 10413.3±0 11012.6±1941 13523.5±1064.7 JK40 18008.1±1075.5 19250±0 39487.2±2820.5 13884.4±6012.1 11899.5±664.9 19738.9±2660.4
- 54 -
Adhesion rate (CFU/cell)
Invasion rate (CFU/cell)
Invasion Index (adhesion bactria/
invasion bacteria)××××100%
Strain
48hr 72hr 48hr 72hr 48hr 72hr
MOI50
Hous 1.032±0.122 0.869±0.246 0.059±0.001 0.101±0.017 5.818±0.774 12.403±5.481 U-4 27.658±4.851 14.048±0.223 0.042±0.021 0.012±0.006 0.16±0.106 0.086±0.039 JK47 14.102±1.289 0.53±0.132 0.015±0.006 0.016±0.003 0.112±0.051 3.178±1.398 JK40 28.457±1.487 11.219±5.901 0.057±0.007 0.011±0.002 0.098±0.025 0.122±0.085 MOI100
Hous 0.378±0.007 3.090±0.336 0.130±0.051 0.339±0.006 48.566±18.858 11.046±1.38 U-4 67.613±13.986 13.111±3.029 0.057±0 0.047±0.009 0.084±0.044 0.36±0.011 JK47 18.147±2.086 2.568±0.123 0.035±0.015 0.05±0.016 0.189±0.064 1.943±0.648 JK40 43.925±2.809 8.014±1.304 0.042±0.011 0.038±0.008 0.057±0.025 0.492±0.178
Strain Protein expression (Western blot) (fold to control)
Bad Bcl-xL Cytochrome c Caspase 9 Caspase 3
MOI50
Control 1±0 1±0 1±0 1±0 1±0
Hous 0.953±0.046 1.31±0.109 0.983±0.069 0.961±0.062 1.002±0.076
U-4 1.213±0.05 0.933±0.052 1.318±0.104 1.218±0.01 1.39±0.132
JK47 1.333±0.046 0.66±0.056 1.208±0.026 1.596±0.026 1.21±0.028
JK40 0.924±0.014 0.9±0.072 0.9±0.134 0.92±0.096 0.869±0.128
圖一:Bartonella spp.在哺乳類宿主的生命週期[31]。
圖二:B. henselae 之 TFSS[30]。
(A)
Hous U4 JK47 JK40
*
Hous U4 JK47 JK40
*
#
圖三:不同 B. henselae 分離株促進 HMEC-1 細胞增生能力之比較。(A) MOI 為 50;(B) MOI 為 100。*:48 小時組間比較 p<0.05;#:72 小時
組間比較 p<0.05
(A)
(B)
圖四:HMEC-1 細胞以顯微鏡觀察之生長情況。(A)為未感染之細胞;(B) Hous 分離株以 MOI50 感染 48 小時後的細胞。
(A)
Bad Bcl-xL Cytochrome c Caspase 9 Caspase 3
Fold
圖六:B. henselae 調控之粒線體內在凋亡路徑。
(A)
Hous U4 JK47 JK40
#
Hous U4 JK47 JK40
*
#
圖七: 不同 B. henselae 分離株抑制細胞凋亡能力之比較。(A) MOI 為 50;
(B) MOI 為 100。*:48 小時組間比較 p<0.05;#:72 小時組間比較 p<0.05。
(A)
(B)
圖八:HMEC-1 細胞經 actinomycin D 刺激凋亡後顯微鏡下之生長情況。
(A) 為僅加入 actinomycin D 之細胞;(B) Hous 分離株以 MOI100 感染 48 小時後的細胞。
(A) (B)
(C) (D)
圖九:不同 B. henselae 分離株之貼附能力比較( 72 小時,稀釋 2000 倍 )。
(A) Hous;(B) U-4;(C) JK47;(D) JK40。
(A) (B)
(C) (D)
圖十:不同 B. henselae 分離株之侵入能力比較( 72 小時,稀釋 20 倍 )。
(A) Hous;(B) U-4;(C) JK47;(D) JK40。
0
Hous U4 JK47 JK40
Adherence rate (CFU/cell)
Hous U4 JK47 JK40
Invasion rate (CFU/cell)
0 20 40 60 80
Hous U4 JK47 JK40
Invasion index(%)
genotypeII (U4 與 JK40)與 genotype I (Hous 與 JK47)比較 p<0.05。
0
Control Hous U4 JK47 JK40
pg/ml
*
*
圖十五:不同 B. henselae 分離株刺激細胞之 SOD 活性比較。*:各分離 株間比較 p<0.05。*:JK47 與其他分離株和控制組比較 p<0.05。
0 10 20 30 40 50
Control Hous U4 JK47 JK40
SOD activity (%)
*
(A) (B)
圖十六:Hous(A)及 U-4(B)分離株間二維電泳分析。
(A) (B)
圖十七:JK47(A)及 JK40(B)分離株間二維電泳分析。
(A) (B)
Hous U4 JK47 JK40
Fold
Hous U4 JK47 JK40
Fold
Hous U4 JK47 JK40
Fold
Hous U4 JK47 JK40
Fold
圖十八(接續下一頁)
(E)
0 0.2 0.4 0.6 0.8 1 1.2
Hous U4 JK47 JK40
Fold
圖十八: 4 個分離株中之 BH-D ( Superoxide dismutase [Cu-Zn ] precursor ) (A)、BU-A ( Acetyl-CoA carboxylase carboxyltransferase subunit alpha ) (B)、BU-B ( Phage related protein ) (C)、47-A (F0F1 ATP synthase subunit
alpha ) (D)與 40-E ( Small heat shock protein ) (E)之 RNA 表現量比較
(A)
(C)
(E)
0 50 100 150 200
24hr 48hr 72hr
Fold
Hous U4 JK47 JK40
圖十九:4 個分離株於感染細胞後之 BH-D ( Superoxide dismutase [Cu-Zn ] precursor ) (A)、BU-A ( Acetyl-CoA carboxylase carboxyltransferase subunit alpha ) (B)、BU-B ( Phage related protein ) (C)、47-A (F0F1 ATP synthase subunit alpha ) (D)與 40-E ( Small heat shock protein ) (E) 之 RNA 表現量比
較。
圖二十:B. henselae 之致病機轉相關蛋白質的功能。
表一:即時聚合酶連鎖反應之引子序列。
Spot Primer Sequence (5’-3’)
47-A-F AGCACCGAGTCGTTTAACACAA 47-A
47-A-R TGGTATGGCACTCAATTTGGAA 40-E-F GCGTTTTCATTTAGCTGATCATGTT 40-E
40-E-R CGGCATTTCTCTTTTAAGCTGAAT BU-A-F GCCAGCCATAGCCTCTAAAGC BU-A
BU-A-R CATTATTCCGGAGCCCTTAGG BU-B-F GCATTTCCGCAGCAGATCA BU-B
BU-B-R CGGCAAGATTGTTGACTTTGG BH-D-F GTGCCGCAGGTGGTCATTAT BH-D
BH-D-R TCGACATACAGTGCTGGTAAGTCA 16S-F GAGAAGAAGCCCCGGCTAAC 16S rRNA
16S-R TATCCGCCTACATGCGCTTT
表二:聚合酶連鎖反應之引子。
Spot Primer Sequence (5’-3’) Length
( bp) 40E-SF TGATGATGAAGGGTTAAGAA
40-E
40E-SR GAGCCATATACGAAACTTCA
825
BUA-SF GCTATCAGCACAAAAGATCC BU-A
BUA-SR TATCGTTTAGTCAATGAACATCA
1336
BUB-SF CCTATGCTAACAAAATCCTTATT BU-B
BUB-SR TCCTCTGTTAATCGCTCTGT
1115
BHD-SF AATAATGGGTGTTTTTGTCG BH-D
BHD-SR AATTTCACCAGTTTGATTGG
971
表三:Hous 及 U-4 經二維電泳分析所得之差異點。
Spot Genebank
Accession No. Protein Description Theoretical Mr/pI BH-D gi|49475620 Superoxide dismutase [Cu-Zn]
precursor
18850/5.87 BH-E gi|49476039 Expressed protein 19684/6.14 BU-A gi|49476285 Acetyl-CoA carboxylase
carboxyltransferase subunit alpha
34927/6.28
BU-B gi|49475174 Phage related protein 29123/5.80 BU-C gi|49475510 Small heat shock protein 19074/5.56
表四:JK47 及 JK40 經二維電泳分析所得之差異點。
Spot Genebank
Accession No. Protein Description Theoretical Mr/pI 47-A gi|49476189 F0F1 ATP synthase subunit
alpha
55477/5.91
47-B gi|49476305 Succinyl-CoA synthetase subunit beta
42790/5.07
47-D gi|49474982 Inorganic pyrophosphatase 20015/5.13
40-C gi|49475012 Peptidyl-prolyl cis-trans isomerase
35575/5.81 40-E
40-F
gi|49475510 Small heat shock protein 19074/5.56
表五:4 個分離株中 5 個表現差異點之蛋白質量與 RNA 表現量比較。 BH-D Superoxide dismutase [Cu-Zn]
precursor
-a 1.5 d
BU-A Acetyl-CoA carboxylase
carboxyltransferase subunit alpha
-b 2 c
表六:4 株分離株間特異蛋白質之核酸及胺基酸序列分析結果。
Similarity (%) Protein
Nucleotide Amino acid
Small heat shock protein 99.6%-100% 100%
Acetyl-CoA carboxylase
carboxyltransferase subunit alpha
99.7%-100% 100%
Phage related protein 99.4%-100% 98.5%-100%
Superoxide dismutase [Cu-Zn ] precursor
98.5%-100% 96.6%-100%