Table of Contents

Chapter 1 7

Chapter 2 39

Chapter 3 61

Chapter 4 77

Chapter 5 89

Chapter 6 125

Chapter 7 145

Chapter 8 161

Chapter 9 181

Addendum 197

203

8

A brief history of the Brachyspiraceae

. .

“a .

9 0.02 (~24bp)

Figure 1:

10

.

Figure 2:

11 Chapter 1

4

.

12

. .

Figure 3:

13 Chapter 1

Chapter 9

The various species

Brachyspira hyodysenteriae (hog: pig; dysentery: severe diarrhoea)

14 * * Type of reference strain* of reference Type + + + + + + + + + + 56 + + + + + + + + + + + + Indole Hippurate Species 44 Table 1: Table

15 B.hyodysenteriae B78 'B.suana

A na' AN 4859/03

B.intermedia PWS/A

B.alvinipulli C1

B.murdochii 56-150 'B.pulli' AN304/04

'B.canis' Dog A2

'B.hampsonii' cluster II NSH-24 B.innocens B256

B.aalborgi 513A

'B.ibaraki' HIS24/11/99

'B.hominis' adhucomuHca09 'B.hampsonii' cluster I NSH-16

'B.muridarum' A58/06

'B.muris' A10/06 'B.corvi' AN968/2/04

us' A249/07

T.primi

B.pilosicoli P43/6/78

'B.ra a ZAS-2

0.03 ‘B.hampsonii’ cluster II NSH-24 B

B.hyodysenteriae B78

‘B.hampsonii’ cluster I NSH-16

B.innocens B256 ‘B.suana

na’ AN 4859/03

B.murdochii 56-150

B.intermedia PWS/A T.primi a ZAS-2

‘B.corvi’ AN968/2/04

B.pilosicoli P43/6/78

B.aalborgi 513A ‘B.canis’ Dog A2

‘B.pulli’ AN304/04

0.04

B.alvinipulli C1 Figure 4: 16

Brachyspira innocens (innocens: innocent) .

Brachyspira murdochii (Murdoch: Australian university where much research into .

Brachyspira pilosicoli (pilo: hairy; colon: colon) chapter 9

17 Chapter 1

Brachyspira intermedia (intemediate: referring to the fact that the phenotype is between B. hyodystenteriae and B. innocens) . . In

Brachyspira alvinipulli

18

Brachyspira aalborgi

‘Brachyspira canis’ (canine: dog) p In

‘Brachyspira corvi’ (corvus: crows)

19 Chapter 1

44

‘Brachyspira pulli’

‘Brachyspira muridarum’ and ‘Brachyspira muris’ . . .

(sus: pig (Anas platyrhynchos))

20

‘Brachyspira hampsonii’ (Prof. Hampson: prominent Brachyspira

‘Brachyspira ibaraki’

21 B. aalborgi B. alvinipullihyodysenteriae B. B. innocens B. intermedia B. murdochii B. pilosicoli ‘B. canis’ ‘B. corvi’ Species Table 2: Table 22 ‘B. hampsonii’ ‘B. hampsonii’ ‘B. hominis’muridarum’ ‘B. ‘B. muris’ ‘B. pulli’ Species

23 Chapter 1

‘Brachyspira hominis’ (hominis: human)

Zoonosis

24

Epidemiological evidence

25 Chapter 1

. . .

26

27 Chapter 1

.

28

Figure 5:

29 Chapter 1

Table 3:

Country Colon biopsies Appendices Faeces*

Concluding

30

Aim of this thesis chapter 2 chapter 4 (chapters 2 8 In chapter 3 Chapter 5 chapter 8. Chapter 6 chapter 7 chapter 5

31 Chapter 1

References 45 88 16 27 12 41 37 17 85 41 8610 70 33 82 36 22 11 34 189 57 11 31 10 40 1 33 31 1 125 50 63 Int J 49 46 3

32

160 Int J 29 53 Int J 47 136 48 178 35 8 36 67 28 59 9 106 14 53 2 130 67 24 Occurrence 7 153 23 15 52 39

33 Chapter 1

146 146 12 158 52 124 121 137 99 37 21 22 102 134 28 46 53 23 35 47 91 111 63 32 23 105 119 15 53 121 59 36

34

41 34 68 153 12 13 16 61 158 42 59 53 21 39 33 2 64 59 65 J 22 J 31 21 J 141 113 113 48 26 138 93 143 146

35 Chapter 1

4 7 103 45 49 31 7 134 30 179 150 49 35 38 30 38 59 224 101 187 21 13 90 39 74 41 23 134 37 Int J 18

36 37 38 4

4

Chapter 2

Abstract

Methods

Results p

Conclusions

40

4

Jensen

41 Chapter 2

.

Aims of this study

42

Methods Ethics statement

43 Chapter 2

Processing of FFPE biopsy samples

44

®

45 Table 1:

Primer set 5’–––3’ Total length °C Time Purpose

PCR volume PCR consumables PCR protocol

46

m ®

Sequencing

StepB (253bp) 203 445 StepA (212bp) StepC (258bp) 60 271 366 623 Bspp (82bp) 135 216 5’ 3’ 0 100 200 300 400 500 600 700

Primer Amplicon

Figure 1:

47 Chapter 2

48

Results A

PCR results p pp

49 12

10

8

6

4

2

0 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96

-2 B. aalborgi) B. pilosicoli)

Figure 2:

Table 2

Sequence result

50 B. burgdorferi B. pilosicoli B. pilosicoli B. murdochii B. innocens B. hyodysenteriae B. intermedia B. alvinipulli Brachyspira ‘B. hominis’ B. aalborgi 0.01 Figure 3:

51 Chapter 2

(p

Table 3: p

# + +

52

Discussion

.

53 Chapter 2

m

54

55 Chapter 2

56

References 48 23 35 53 160 42 2 16 Int J 46 31 40 49 7 67 63 106 41 62 115 41 12 16 2 12 39 53 59 116 39

57 Chapter 2

197 25 Suppl 3 37 27 12 132 83 95 32 23 40 67 136 178 35

58 Supplementary Table S1:

59 60

Chapter 3

Abstract

Methods

Results

Conclusion

62 Appendiceal Spirochaetosis in Children

.

.

63 Chapter 3

.

64 Appendiceal Spirochaetosis in Children

Materials and methods Ethics statement

Sample processing

65 Chapter 3

®

®

66 Table 1:

5’–––3’ Amplicon

PCR volume PCR protocol

67 Chapter 3

Histopathology

®®

68 Appendiceal Spirochaetosis in Children

Results

Table 2: Immunohistochemistry

PCR result ++++++

p

(p

69 Chapter 3

Discussion

Table 3: Total appendices Control group Other diagnoses 4

70 Appendiceal Spirochaetosis in Children

(p

71 Chapter 3

®

72 Appendiceal Spirochaetosis in Children

References 24 17 39 12 53 27 88 39 90 23 23 8 154 3 52 16 J 38 7 53 160 4 67 31 35 Am J 132 2 55 142 25 Suppl 3 2 51 59 7

73 Chapter 3

37 33 65

74 75 76 4

4

Chapter 4

Abstract (p

78

As a

79 Chapter 4

Materials and methods ® ®

Table 1:a

a

80

Results p

p

81 Chapter 4

Discussion

p

82

83 Chapter 4

84

References 16 48 3 85 7 101 53 21 23 21 59 39 2 70 J 22 82 45 22 82 53 4 132 53 31 J 38 42 16 31 7

85 Supplementary table S1: Sample ID .etrc .jjn S. dysenteriae C. jejuni S. enterica + + * * * + * * STEC/EPEC + + + + G. lamblia + + + Parasites .faii C. parvum D. fragilis * * # + +

86 87 88 A 4

4

Chapter 5

Abstract

90

Brachyspira species . (

91 Chapter 5

. In (alp

.

92

Material and methods MLST design

Table 1:

Criterion Database

93 Chapter 5

®

atpG

94

atpG

95 Table 2:

Amplicon (bp) Locus Target Primers** Total Useful Min

atpG

® PCR volume PCR consumables PCR protocol

96 0.02 (~24bp)

Colour-plate A: Colour-plate B: Colour-plate C: 12

10

8

6

4

2

0 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96

-2

513A (B. aalborgi) WesB (B. pilosicoli)

Colour-plate D: 12

10

8

6

4

2

0 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96

-2

513A (B. aalborgi) WesB (B. pilosicoli)

Colour-plate E: B. aalborgi ‘B. hominis’ B. murdochii B. innocens

B. pilosicoli B. hyodysenteriae B. alvinipulli B. intermedia

Colour-plate F: B. innocens B. aalborgi ‘B. hominis’ B. murdochii B. innocens

B. intermedia B. pilosicoli B. hyodysenteriae B. alvinipulli B. intermedia

Colour-plate G:

Colour-plate H:

Colour-plate I: WA1 B-78 PWS/A Q98.0033.72 513A 56-150 C1 T.primitia_ZAS-2 T1 199800660 200517505 Q97.2110.4.11 WesB OF_11 WF1 K1 201101966 201009139 201102362 200909930 200831665 VTN021f HRM_4B HRM_2B N1 RV1 SC1 Q94.0354.0.6 Q98.0037.6 7072i L72 201013692 200300944 200410620a 200410620b 200709033 200513182a 200513182b 200900828 201009156 200232081 201105386 201204927 201221374 201200678 VTN022f f199600014 D9201243 Q1404.6A 3295.90B HRM7A W015/C138 WW25 WIA8 HRM7 Q95.0635.6 Q95.2078.2 Q95.3281.0 H60-2 Q97.2224.3.1 Q98.0028.3 Q98.0072.31 Q97.000.6.8 Q98.0026.12 Q98.0072.08 H38-2 H4-2 J_F2 QF1 EM1 KP5 Human M1 Q1588.5 9803.1 Pig V1_H141 95/1000 Q91.1223.3 B256 Chicken P43/6/78 201124725 201125230 Dog 200805431 V1_H11 H21

0.05

Colour-plate J: WA1 B-78 PWS/A 56-150 B256 C1 T.primitia_ZAS-2 513A 201101966 T1 Q97.2110.4.11 Q95.0635.6 Q1588.5 9803.1 P43/6/78 A Q91.1223.3 W015/C138 WW25 KP5 WesB OF_11 B WF1 K1 200909930 HRM_4B HRM_2B HRM7A HRM7 N1 RV1 SC1 200517505 200300944 201204927 7072i 201124725 201105386 200513182a 200513182b EM1 200232081 201009156 V1_H141 Q94.0354.0.6 201221374 V1_H11 QF1 201125230 201013692 200900828 200410620a 200410620b 201200678 200805431 95/1000 H60-2 Q97.2224.3.1 C Q98.0072.08 M1 201009139 200709033 201102362 200831665 VTN021f VTN022f JF2 Human H21 WIA8 Q98.0072.31 Pig Q98.0026.12 3295.90B Q95.2078.2 Q98.0028.3 Chicken D9201243 Q1404.6A H38-2 Dog H4-2 Q95.3281.0 Q97.000.6.8 0.05

Colour-plate K: The Netherlands Italy United Kingdom

Human Chicken Pig Dog Australia Papua New Guinea United States of America

Colour-plate L: The Netherlands Italy United Kingdom

Australia Papua New Guinea United States of America

Colour-plate M: Groningen SIR biopsies: 0.89 (0.88 - 0.90) SIR HIS: 0.29 (0.13 - 0.55) Pigs 63.7/km2 Poultry 2.376.6/km2 HIV-centres 1/30

Noord-Holland SIR biopsies: 1.01 (1.01 - 1.02) SIR HIS: 1.84 (1.63 - 2.08) Pigs 9.7/km2 2 Poultry 493.4/km Friesland HIV-centres 9/30 SIR biopsies: 1.04 (1.02 - 1.05) SIR HIS: 0.21 (0.08 - 0.42) Pigs 31.8/km2 Poultry 2,187.2/km2 Drenthe HIV-centres 1/30 SIR biopsies: 0.92 (0.90 - 0.93) Flevoland SIR HIS: 0.54 (0.29 - 0.90) SIR biopsies: 1.20 (1.18 - 1.22) Pigs 107,5/km2 SIR HIS: 2.24 (1.62 - 3.02) Poultry 2,363.8/km2 Pigs 40.8/km2 HIV-centres 0/30 Poultry 1,461.9/km2 Overijssel HIV-centres 2/30 SIR biopsies: 0.94 (0.93 - 0.95) SIR HIS: 0.96 (0.72 - 1.24) Pigs 483.2/km2 Poultry 2,943.3/km2 HIV-centres 2/30 Utrecht SIR biopsies: 0.97 (0.96 - 0.98) SIR HIS: 0.93 (0.71 - 1.20) Pigs 219.1/km2 Poultry 1,227.9/km2 HIV-centres 2/30 Gelderland SIR biopsies: 1.08 (1.08 - 1.09) SIR HIS: 0.48 (0.36 - 0.64) Pigs 442.9/km2 Zuid-Holland 2 SIR biopsies: 0.99 (0.98 - 0.99) Poultry 3,439.3/km SIR HIS: 0.46 (0.37 - 0.57) HIV-centres 2/30 Pigs 56.5/km2 Poultry 390.0/km2 HIV-centres 7/30

Noord-Brabant SIR biopsies: 0.82 (0.81 - 0.82) SIR HIS: 0.58 (0.46 - 0.73) Limburg Pigs 1,078.6/km2 SIR biopsies: 1.27 (1.26 - 1.28) 2 SIR HIS: 2.92 (2.51 - 3.38) Poultry 5,330.5/km 2 HIV-centres 2/30 Pigs 790.6/km Poultry 6,880.0/km2 HIV-centres 1/30

Zeeland SIR biopsies: 0.86 (0.85 - 0.88) SIR HIS: 1.03 (0.64 - 1.58) Pigs 43.6/km2 Poultry 1,015.2/km2 HIV-centres 1/30

Colour-plate N: 4 4

Groningen SIR biopsies: 0.89 (0.88 - 0.90) SIR HIS: 0.29 (0.13 - 0.55) Pigs 63.7/km2 Poultry 2.376.6/km2 HIV-centres 1/30 3 5 3 5 Noord-Holland SIR biopsies: 1.01 (1.01 - 1.02) A C SIR HIS: 1.84 (1.63 - 2.08) Pigs 9.7/km2 2 Poultry 493.4/km Friesland HIV-centres 9/30 SIR biopsies: 1.04 (1.02 - 1.05) SIR HIS: 0.21 (0.08 - 0.42) 2 1 2 1 Pigs 31.8/km2 Poultry 2,187.2/km2 Drenthe 6 6 HIV-centres 1/30 SIR biopsies: 0.92 (0.90 - 0.93) Flevoland SIR HIS: 0.54 (0.29 - 0.90) 7 7 SIR biopsies: 1.20 (1.18 - 1.22) Pigs 107,5/km2 SIR HIS: 2.24 (1.62 - 3.02) Poultry 2,363.8/km2 Pigs 40.8/km2 HIV-centres 0/30 Poultry 1,461.9/km2 Overijssel HIV-centres 2/30 SIR biopsies: 0.94 (0.93 - 0.95) SIR HIS: 0.96 (0.72 - 1.24) Pigs 483.2/km2 Poultry 2,943.3/km2 HIV-centres 2/30 4 4 Utrecht SIR biopsies: 0.97 (0.96 - 0.98) SIR HIS: 0.93 (0.71 - 1.20) Pigs 219.1/km2 Poultry 1,227.9/km2 HIV-centres 2/30 Gelderland SIR biopsies: 1.08 (1.08 - 1.09) SIR HIS: 0.48 (0.36 - 0.64) Pigs 442.9/km2 3 3 Zuid-Holland 2 SIR biopsies: 0.99 (0.98 - 0.99) Poultry 3,439.3/km 5 5 SIR HIS: 0.46 (0.37 - 0.57) HIV-centres 2/30 Pigs 56.5/km2 B D Poultry 390.0/km2 HIV-centres 7/30

Noord-Brabant 2 1 2 1 SIR biopsies: 0.82 (0.81 - 0.82) SIR HIS: 0.58 (0.46 - 0.73) Limburg 6 6 Pigs 1,078.6/km2 SIR biopsies: 1.27 (1.26 - 1.28) 2 SIR HIS: 2.92 (2.51 - 3.38) Poultry 5,330.5/km 2 HIV-centres 2/30 Pigs 790.6/km 7 7 Poultry 6,880.0/km2 HIV-centres 1/30

1 Appendix Zeeland SIR biopsies: 0.86 (0.85 - 0.88) 2 Coecum SIR HIS: 1.03 (0.64 - 1.58) Pigs 43.6/km2 3 Ascending colon Poultry 1,015.2/km2 HIV-centres 1/30 4 Transversing colon 5 Descending colon 6 Sigmoid 7 Rectum

Colour-plate O: A

B

Colour-plate P:

Results Selected MSLT genes (atpG

atpG

97 201105351b_B.aalborgi igroblaa.B_d153501102

igroblaa.B_e153501102

igroblaa.B_f153501102

201024610_B.aalborgi

201150471_B.aalborgi

201202009_B.aalborgi

201023408_B.aalborgi 201022967i_B.aalborgi

201022967h_B.aalborgi

201022967g_B.aalborgi

201022967f_B.aalborgi

201022967e_B.aalborgi

201022967d_B.aalborgi

201022967c_B.aalborgi

igroblaa.B_c153501102

igroblaa.B_a153501102

201105351g_B.aalborgi 201022967b_B.aalborgi 201111603_B.aalborgi

201114303_B.aalborgi

201123898_B.aalborgi

200101917_B.aalborgi 200918072_B.aalborgi 201150177_B.aalborgi

201104406_B.aalborgi 200917097_B.aalborgi 201050465_B.aalborgi

201014350_B.aalborgi 201015580_B.aalborgi 201040076_B.aalborgi

200813138g_B.aalborgi 200216407_B.aalborgi

200707443_B.aalborgi 200813138f_B.aalborgi 201050211_B.aalborgi

200813138e_B.aalborgi 201024300_B.aalborgi

200922746_B.aalborgi 200813138d_B.aalborgi 200113332_B.aalborgi 200813138c_B.aalborgi 200414761_B.aalborgi

200813138b_B.aalborgi 513A_B.aalborgi

201104608_B.aalborgi 200813138a_B.aalborgi 200813340_B.aalborgi

200805639_B.aalborgi 200501138_B.aalborgi

200709653_B.aalborgi 200904021_B.aalborgi

201103059_B.aalborgi 200914805_B.aalborgi 201120460_B.aalborgi 201150471_B.aalborgi 200602985_B.aalborgi 201003249_B.aalborgi 200900639_B.aalborgi 200900639_B.aalborgi 201110374a_B.aalborgi

201104140_B.hominis 201001908*_B.aalborgi 201110374b_B.aalborgi

201110374d_B.aalborgi 200923973_B.aalborgi 201104149_B.aalborgi 201110374g_B.aalborgi 200430368_B.aalborgi 201102752_B.aalborgi 200902757_B.aalborgi 201129345_B.aalborgi 201129345_B.aalborgi 200702703_B.aalborgi 200608126*_B.hominis 201109833_B.aalborgi 200624827_B.aalborgi

200805639_B.aalborgi 200920244_B.aalborgi 200704900_B.aalborgi

200917337_B.aalborgi 200813138c_B.aalborgi 200430368_B.aalborgi 95/1000_GenBank_B.pilosicoli WesB_B.pilosicoli 200813138f_B.aalborgi 200716125_B.aalborgi P43/6/78_B.pilosicoli ilocisolip.B_502306991 ilocisolip.B_566138002 200917097_B.aalborgi 201113577_B.aalborgi 200513182a_B.pilosicoli 200513182b_B.pilosicoli ilocisolip.B_032521102 ilocisolip.B_669101102 201022967c_B.aalborgi 201122669_B.aalborgi 200232081_B.pilosicoli ilocisolip.B_263201102 ilocisolip.B_683501102 201022967f_B.aalborgi 201108681_B.aalborgi 200410620a_B.pilosicoli 200410620b_B.pilosicoli 201022967g_B.aalborgi 200923973_B.aalborgi 201013692_B.pilosicoli ilocisolip.B_039909002 ilocisolip.B_828009002 201022967d_B.aalborgi 200913478_B.aalborgi ilocisolip.B_931900102 ilocisolip.B_449003002 200918072_B.aalborgi 200901135_B.aalborgi ilocisolip.B_505715002 ilocisolip.B_729402102 200813138g_B.aalborgi 201111933_B.aalborgi ilocisolip.B_651900102 ilocisolip.B_473122102 ilocisolip.B_876002102 200813138d_B.aalborgi 200816817_B.aalborgi ilocisolip.B_134508002

200901634_B.aalborgi 200813138a_B.aalborgi ilocisolip.B_527421102 ilocisolip.B_330907002 201122867_B.aalborgi

201129144_B.aalborgi

201004769_B.aalborgi

C1_B.alvinipulli B256_B.innocens 201018213_B.aalborgi 56-150_B.murdochii PWS/A_B.intermedia WA1_GenBank_B.hyodysenteriae B-78_B.hyodysenteriae 200808214_B.aalborgi ilocisolip.B_066008991

200703075_B.aalborgi

200813138h_B.aalborgi

201119045_B.aalborgi

201024466_B.aalborgi

201124639_B.aalborgi

201007259_B.aalborgi

200811646_B.aalborgi sinimoh.B_b295300102 200925995_B.hominis

200803874_B.hominis sinimoh.B_115509002

sinimoh.B_207415002

sinimoh.B_343806002

201021258_B.hominis

201104140_B.hominis

200608126*_B.hominis 201024348_B.hominis

201003592a_B.hominis

201003592c_B.hominis

201003592d_B.hominis

201003592e_B.hominis sinimoh.B_300706002

sinimoh.B_566207002 201108603_B.hominis sinimoh.B_700611102

T.primitia_ZAS-2

0.05

Figure 1: 19

98 igroblaa.B_009407002

igroblaa.B_441921102

201004769_B.aalborgi

201050465_B.aalborgi sinimoh.B_843420102

201150177_B.aalborgi

200914805_B.aalborgi

200816817_B.aalborgi

200913478_B.aalborgi

201113577_B.aalborgi

201109833_B.aalborgi

201104149_B.aalborgi

sinimoh.B_478308002 200607003_B.hominis igroblaa.B_307207002

igroblaa.B_831105002 201023408_B.aalborgi 200813138b_B.aalborgi 201024610_B.aalborgi

201105351b_B.aalborgi 200813138e_B.aalborgi 201105351c_B.aalborgi 201105351d_B.aalborgi

201105351e_B.aalborgi 200813138h_B.aalborgi 201105351f_B.aalborgi

201105351g_B.aalborgi 201022967b_B.aalborgi 201111603_B.aalborgi

201022967e_B.aalborgi 201114303_B.aalborgi

200101917_B.aalborgi 201022967i_B.aalborgi 201007259_B.aalborgi

200716125_B.aalborgi 201040076_B.aalborgi

201119045_B.aalborgi 200702665_B.hominis

201003592a_B.hominis 201123898_B.aalborgi 201003592b_B.hominis

201105351a_B.aalborgi 201003592c_B.hominis

201003592d_B.hominis 201122867_B.aalborgi 201003592e_B.hominis

200608343_B.hominis 201104608_B.aalborgi

200813340_B.aalborgi 200113332_B.aalborgi

200901634_B.aalborgi 201021258_B.hominis 200905511_B.hominis 201104406_B.aalborgi 201103059_B.aalborgi i 201150471_B.aalborgi 201120460_B.aalborgi 201003249_B.aalborgi i 200900639_B.aalborgi 201124639_B.aalborgi 201110374a_B.aalborg 201110374a_B.aalborgi borgi 201110374b_B.aalborg 201104140_B.hominis 201110374b_B.aalborgi 201110374d_B.aalalborgi 200923973_B.aalborgi 201110374d_B.aalborgi 201110374g_B.a i 200430368_B.aalborgi 201110374g_B.aalborgi 200902757_B.aalborg i 201129345_B.aalborgi 200902757_B.aalborgi 200702703_B.aalborg i 200608126*_B.hominis 200216407_B.aalborgi 200624827_B.aalborg i 201108603_B.hominis 200704900_B.aalborg 200805639_B.aalborgi i 513A_B.aalborgi 200917337_B.aalborg 200813138c_B.aalborgi WA1_GenBank_B.hyodysenteriae B-78_B.hyodysenteriae 200813138f_B.aalborgi

ilocisolip.B_066008991 200917097_B.aalborgi ilocisolip.B_828009002

200410620a_B.pilosicoliilocisolip.B_296310102 201022967c_B.aalborgi 200410620b_B.pilosicoliilocisolip.B_032521102

201022967f_B.aalborgi

201009139_B.pilosicoli 201022967g_B.aalborgi ilocisolip.B_651900102 ilocisolip.B_876002102

201022967d_B.aalborgi 95/1000_GenBank_B.pilosicoli ilocisolip.B_134508002 P43/6/78_B.pilosicoli

200918072_B.aalborgi ilocisolip.B_330907002 200513182a_B.pilosicoli ilocisolip.B_566138002 200513182b_B.pilosicoli 200813138g_B.aalborgi ilocisolip.B_263201102

200813138d_B.aalborgi

ilocisolip.B_180232002 200813138a_B.aalborgi ilocisolip.B_473122102 201024466_B.aalborgi WesB_B.pilosicoli

200602985_B.aalborgi i ilocisolip.B_683501102

ilocisolip.B_527421102 201102752_B.aalborgi C1_B.alvinipulli

ilocisolip.B_039909002

ilocisolip.B_502306991 200920244_B.aalborg B256_B.innocens ilocisolip.B_729402102

ilocisolip.B_449003002 PWS/A_B.intermedia ilocisolip.B_505715002

201122669_B.aalborgi ilocisolip.B_669101102

56-150_B.murdochii 201111933_B.aalborgi

200917337_B.aalborgi

201015580_B.aalborgi

201116007_B.hominis

201050211_B.aalborgi

200925995_B.hominis

200514702_B.hominis

201003249_B.aalborgi

200624827_B.aalborgi

200811646_B.aalborgi

igroblaa.B_647229002 igroblaa.B_*809100102

201014350_B.aalborgi

201018213_B.aalborgi

201024300_B.aalborgi

200414761_B.aalborgi

200808214_B.aalborgi

201022967h_B.aalborgi

200709653_B.aalborgi 201202009_B.aalborgi

201108681_B.aalborgi igroblaa.B_570307002

200707443_B.aalborgi igroblaa.B_531109002

200904021_B.aalborgi

T.primitia_ZAS-2

0.06

Figure 2:

99 igroblaa.B_053410102 igroblaa.B_936421102

200702703_B.aalborgi

201111603_B.aalborgi

200917337_B.aalborgi

201104140_B.hominis 201003592b_B.hominis

201003592c_B.hominis

201003592d_B.hominis

200803874_B.hominis

201021258_B.hominis

201150177_B.aalborgi 200904021_B.aalborgi 200905511_B.hominis igroblaa.B_941401102 sinimoh.B_843420102 200923973_B.aalborgi

200925995_B.hominis 200602985_B.aalborgi

200805639_B.aalborgi200922746_B.aalborgi 201111933_B.aalborgi 201123898_B.aalborgi

201105351c_B.aalborgi 200920244_B.aalborgi 201105351b_B.aalborgi

201105351d_B.aalborgi 200624827_B.aalborgi

200811646_B.aalborgi 200414761_B.aalborgi

201103059_B.aalborgi

201015580_B.aalborgi 513A_B.aalborgi 200707443_B.aalborgi 201007259_B.aalborgi 201108681_B.aalborgi

200808214_B.aalborgi 200709653_B.aalborgi

200914805_B.aalborgi 201119045_B.aalborgi 201102752_B.aalborgi 200816817_B.aalborgi 201129345_B.aalborgi 200702665_B.hominis 200813138a_B.aalborgi 200904021_B.aalborgi 200608343_B.hominis 200813138g_B.aalborgi 201003249_B.aalborgi 200704900_B.aalborgi 200514702_B.hominis 200430368_B.aalborgi 200813138c_B.aalborgi 200716125_B.aalborgi 201116007_B.hominis 200113332_B.aalborgi 201113577_B.aalborgi 201003249_B.aalborgi 200501138_B.aalborgi 201122669_B.aalborgi

201129144_B.aalborgi 201050211_B.aalborgi 201108681_B.aalborgi 201122669_B.aalborgi 200902757_B.aalborgi 200923973_B.aalborgi WA1_GenBank_B.hyodysenteriae B-78_B.hyodysenteriae 200816817_B.aalborgi 201114303_B.aalborgi PWS/A_B.intermedia 200917337_B.aalborgi 201024610_B.aalborgi C1_B.alvinipulli 200914805_B.aalborgi 56-150_B.murdochii 201018213_B.aalborgi B256_B.innocens 201015580_B.aalborgi

200900639_B.aalborgi 201202009_B.aalborgi

201150471_B.aalborgi 200913478_B.aalborgi 201150177_B.aalborgi P43/6/78_B.pilosicoliilocisolip.B_669101102 201104406_B.aalborgi 201116007_B.hominis

201104406_B.aalborgi

200513182a_B.pilosicoli 200918072_B.aalborgi 201050465_B.aalborgi ilocisolip.B_473122102 200513182b_B.pilosicoli

200716125_B.aalborgi201050465_B.aalborgi ilocisolip.B_180232002

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201024300_B.aalborgi

2 ilocisolip.B_505715002 201104608_B.aalborgi ilocisolip.B_449003002

201202009_B.aalborgi 95/1000_GenBank_B.pilosicoli

201022967d_B.aalborgi ilocisolip.B_039909002

ilocisolip.B_566138002 ilocisolip.B_263201102

201022967c_B.aalborgi ilocisolip.B_330907002 ilocisolip.B_683501102

200813138e_B.aalborgi ilocisolip.B_52742110

200901135_B.aalborgi ilocisolip.B_729402102 200813138d_B.aalborgi 201150471_B.aalborgi ilocisolip.B_032521102

ilocisolip.B_296310102 201022967e_B.aalborgi 200917097_B.aalborgi

201110374d_B.aalborgi ilocisolip.B_828009002

201110374b_B.aalborgi

ilocisolip.B_931900102

ilocisolip.B_134508002 ilocisolip.B_651900102

ilocisolip.B_876002102

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T.primitia_ZAS-2 0.06 Figure 3:

100 igroblaa.B_806401102

sinimoh.B_e295300102

201040076_B.aalborgi

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200703075_B.aalborgi

200101917_B.aalborgi

201123898_B.aalborgi

201114303_B.aalborgi

200501138_B.aalborgi

_599529002

201022967h_B.aalborgi200514702_B.hominis

201022967g_B.aalborgi

201022967d_B.aalborgi

sinimoh.B_d295300102 sinimoh.B

igroblaa.B_647229002 201022967c_B.aalborgi 200813340_B.aalborgi 201124639_B.aalborgi

201110374a_B.aalborgi

201110374b_B.aalborgi

201110374d_B.aalborgi 200608343_B.hominis 201110374g_B.aalborgi 200902757_B.aalborgi

201129144_B.aalborgi 200803874_B.hominis 513A_B.aalborgi

200917097_B.aalborgi 200900639_B.aalborgi

200901135_B.aalborgi 200813138h_B.aalborgi 201018213_B.aalborgi

200813138g_B.aalborgi 200913478_B.aalborgi

200608126*_B.hominis 200813138f_B.aalborgi 200602985_B.aalborgi

200813138c_B.aalborgi 200805639_B.aalborgi

200813138a_B.aalborgi 200813138b_B.aalborgi 200813138d_B.aalborgi

200709653_B.aalborgi 200813138e_B.aalborgi

201022967i_B.aalborgi 200607003_B.hominis 201023408_B.aalborgi 201001908*_B.aalborgi 201105351a_B.aalborgi

201104149_B.aalborgi 201105351b_B.aalborgi

201105351c_B.aalborgi 201102752_B.aalborgi i 201105351d_B.aalborgi 201129345_B.aalborgi 201105351g_B.aalborgi 200813138a_B.aalborgi i 200904021_B.aalborgi 201111603_B.aalborgi 200813138g_B.aalborg 201003249_B.aalborgi 200808214_B.aalborgi i 200704900_B.aalborg 201007259_B.aalborgi 200430368_B.aalborgi 200813138c_B.aalborgi 200811646_B.aalborgi 200716125_B.aalborgi 201003592a_B.hominis 200113332_B.aalborg i 201113577_B.aalborgi 201003592b_B.hominis 200501138_B.aalborg i 201122669_B.aalborgi 201003592c_B.hominis 201050211_B.aalborg 201108681_B.aalborgi 200901634_B.aalborgi i 201122669_B.aalborg 200905511_B.hominis 200923973_B.aalborgi 200805431_B.pilosicoli 95/1000_GenBank_B.pilosicoli 200816817_B.aalborgi P43/6/78_B.pilosicoli

200831665_B.pilosicoli ilocisolip.B_931900102 200917337_B.aalborgi ilocisolip.B_330907002 ilocisolip.B_263201102 200914805_B.aalborgi

ilocisolip.B_180232002 201015580_B.aalborgi 200900828_B.pilosicoli 200410620b_B.pilosicoliilocisolip.B_473122102 200410620a_B.pilosicoli 201202009_B.aalborgi ilocisolip.B_876002102

21102 ilocisolip.B_651900102 201150471_B.aalborgi 200513182b_B.pilosicoli 200513182a_B.pilosicoli 201150177_B.aalborgi 201101966_B.pilosicoli 201024466_B.aalborgi ilocisolip.B_296310102 WesB_B.pilosicoli 201116007_B.hominis ilocisolip.B_0325 ilocisolip.B_502306991 ilocisolip.B_039909002 201104406_B.aalborgi ilocisolip.B_729402102 ilocisolip.B_683501102 201050465_B.aalborgi

ilocisolip.B_449003002 WA1_GenBank_B.hyodysenteriae 201021258_B.hominis B-78_B.hyodysenteriae ilocisolip.B_505715002

ilocisolip.B_527421102 201004769_B.aalborgi

200113332_B.aalborgi PWS/A_B.intermedia

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200216407_B.aalborgi

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igroblaa.B_728426002

201105351e_B.aalborgi 201024610_B.aalborgi 201024348_B.hominis

201022967f_B.aalborgi

201022967e_B.aalborgi

201022967b_B.aalborgi 200918072_B.aalborgi

201109833_B.aalborgi

200920244_B.aalborgi

201111933_B.aalborgi

201024300_B.aalborgi igroblaa.B_009407002

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T.primitia_ZAS-2

0.06

Figure 4:

101 201114303_B.aalborgi

igroblaa.B_646118002 201104149_B.aalborgi

200917337_B.aalborgi

200501138_B.aalborgi

200702703_B.aalborgi

201050211_B.aalborgi

201122669_B.aalborgi

201018213_B.aalborgi

200900639_B.aalborgi

200913478_B.aalborgi

200624827_B.aalborgi

201105351d_B.aalborgi 513A_B.aalborgi

200902757_B.aalborgi

201129144_B.aalborgi

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201105351b_B.aalborgi 201124639_B.aalborgi

200702665_B.hominis

200707443_B.aalborgi 201123898_B.aalborgi 201024610_B.aalborgi

201111603_B.aalborgi 200922746_B.aalborgi 200813138c_B.aalborgi

201105351c_B.aalborgi 200813138g_B.aalborgi

200709653_B.aalborgi

200805639_B.aalborgi 200813138a_B.aalborgi

200923973_B.aalborgi 201150177_B.aalborgi 201108681_B.aalborgi

201021258_B.hominis 200914805_B.aalborgi

200816817_B.aalborgi 200925995_B.hominis 201104406_B.aalborgi 200803874_B.hominis 201116007_B.hominis

201015580_B.aalborgi 200113332_B.aalborgi

201119045_B.aalborgi 201024300_B.aalborgi

200514702_B.hominis 200602985_B.aalborgi 200414761_B.aalborgi 200920244_B.aalborgi 200704900_B.aalborgi

201111933_B.aalborgi 201003249_B.aalborgi

201104140_B.hominis 200904021_B.aalborgi

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200808214_B.aalborgi 56-150__B.murdochii B256_B.innocens 201024348_B.hominis C1_B.alvinipulli

200905511_B.hominis

201003592d_B.hominis 201110374b_B.aalborgi

201003592c_B.hominis 201110374d_B.aalborgi

201003592b_B.hominis T.primitia_ZAS-2

201050465_B.aalborgi

201122867_B.aalborgi 200909930_B.pilosicoli ilocisolip.B_669101102

200813138e_B.aalborgi 201009156_B.pilosicoli 200813138d_B.aalborgi

201022967c_B.aalborgi ilocisolip.B_180232002

201022967d_B.aalborgi

201022967e_B.aalborgi ilocisolip.B_828009002

201104608_B.aalborgi WesB_B.pilosicoli ilocisolip.B_296310102 201202009_B.aalborgi 200513182b_B.pilosicoli ilocisolip.B_032521102 200901135_B.aalborgi 200513182a_B.pilosicoli 201150471_B.aalborgi 200918072_B.aalborgi 200917097_B.aalborgi 200716125_B.aalborgi ilocisolip.B_527421102

ilocisolip.B_134508002 200410620a_B.pilosicoli

ilocisolip.B_931900102

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ilocisolip.B_876002102

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95/1000_GenBank_B.pilosicoli

ilocisolip.B_330907002 0.06 Figure 5:

102

atpG

Table 3:

Length Locus MLST Length (bp) AAT variable sites variable sites

atpG

T.primitia_Z AS-2 **

103 B. aalborgi B. pilosicoli B. murdochii B. innocens

‘B. hominis’ B. hyodysenteriae B. alvinipulli B. intermedia

Figure 6:

104 B. aalborgi B. pilosicoli B. murdochii B. innocens

B. hyodysenteriae B. intermedia ‘B. hominis’ B. alvinipulli B. intermedia

Figure 7:

105 Chapter 5

106

Figure 8:

107 Chapter 5

Discussion

108

As

atpG .

109 Chapter 5

.

110

111 Chapter 5

References 32 2 4 154 36 52 39 J 38 16 36 7 3 53 77 53 153 23 43 136 14 12 5 43 2 62

112

4 138 1 7 102 13 95 29 51 27 12 23 28 13 67 41 132 39

113 201104140_B.hominis

igroblaa.B_863034002 201111933_B.aalborgi 201104608_B.aalborgi igroblaa.B_775311102

201103059_B.aalborgi 201109833_B.aalborgi

200608126*_B.hominis

200918072_B.aalborgi

201024348_B.hominis 201003592a_B.hominis

201003592b_B.hominis

sinimoh.B_599529002 201003592c_B.hominis sinimoh.B_478308002

igroblaa.B_936508002 201003592d_B.hominis igroblaa.B_412808002

200923973_B.aalborgi

200917337_B.aalborgi

201202009_B.aalborgi 201003592e_B.hominis 201150177_B.aalborgi 201122867_B.aalborgi

201150471_B.aalborgi 201104406_B.aalborgi 200902757_B.aalborgi

200905511_B.hominis 200702665_B.hominis

201110374a_B.aalborgi 200703075_B.aalborgi

200813138h_B.aalborgi

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200901135_B.aalborgi 201110374d_B.aalborgi 201116007_B.hominis

201110374g_B.aalborgi 201024300_B.aalborgi

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201022967c_B.aalborgi 201124725_B.pilosicoli ilocisolip.B_729402102 201003592c_B.hominis 200831665_B.pilosicoli 200813138g_B.aalborgi ilocisolip.B_330907002 200905511_B.hominis ilocisolip.B_263201102 200813138f_B.aalborgi 200513182a_B.pilosicoliilocisolip.B_651900102 200901634_B.aalborgi 200513182b_B.pilosicoliilocisolip.B_180232002 200813138e_B.aalborgi ilocisolip.B_134508002 WesB_B.pilosicoli ilocisolip.B_669101102 201015580_B.aalborgi P43/6/78_B.pilosicoli 199603205_B.pilosicoli 200813138d_B.aalborgi 201119045_B.aalborgi

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200813138b_B.aalborgi 201122867_B.aalborgi

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ilocisolip.B_032521102 201129345_B.aalborgi 201104608_B.aalborgi ilocisolip.B_296310102

ilocisolip.B_931900102 201122669_B.aalborgi ilocisolip.B_449003002 201007259_B.aalborgi ilocisolip.B_473122102

201108681_B.aalborgi 201102752_B.aalborgi 200816817_B.aalborgi

200914805_B.aalborgi

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B-78_B.hyodysenteriae 200904021_B.aalborgi B256_B.innocens

igroblaa.B_064021102

200716125_B.aalborgi

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201105351d_B.aalborgi

aidemretni .B_A/SWP

102

airetnsdy B_knaBneG_1AW . nesydoyh t e r i ea

T.primitia_ZAS-2

0.06

114 igroblaa.B_942300102

201024300_B.aalborgi sinimoh.B_343806002

200913478_B.aalborgi sinim

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201111603_B.aalborgi

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201105351c_B.aalborgi 200704900_B.aalborgi

200716125_B.aalborgi 200501138_B.aalborgi

200113332_B.aalborgi

200917337_B.aalborgi 201050211_B.aalborgi

201110374g_B.aalborgi 200914805_B.aalborgi

200816817_B.aalborgi 201004769_B.aalborgi 201108681_B.aalborgi

200925995_B.hominis 201122669_B.aalborgi

201129345_B.aalborgi 200803874_B.hominis

200709653_B.aalborgi 200624827_B.aalborgi 200813138a_B.aalborgi

200608126*_B.hominis 200813138c_B.aalborgi

200813138d_B.aalborgi 201109833_B.aalborgi

200813138e_B.aalborgi 200920244_B.aalborgi 200920244_B.aalborgi 200813138f_B.aalborgi 201040076_B.aalborgi 201111933_B.aalborgi i 200813138g_B.aalborgi 200811646_B.aalborgi 201104140_B.hominis 201022967b_B.aalborgi i 201104149_B.aalborg 201021258_B.hominis 201022967c_B.aalborgi 201007259_B.aalborg i 201022967d_B.aalborgi 201024348_B.hominis 201124639_B.aalborg i 201022967e_B.aalborgi 200918072_B.aalborgi 201014350_B.aalborg i 201022967f_B.aalborgi 201050465_B.aalborg 201003592b_B.hominis 201022967g_B.aalborgi i 200624827_B.aalborg 201003592a_B.hominis 201022967h_B.aalborgi i 200414761_B.aalborg 201003592d_B.hominis 201022967i_B.aalborgi

201003592c_B.hominis 200813340_B.aalborgi

201108603_B.hominis 200905511_B.hominis

201024610_B.aalborgi 200901634_B.aalborgi

WA1_GenBank_B.hyodysenteriae B-78_B.hyodysenteriae 201015580_B.aalborgi PWS/A_B.intermedia

201119045_B.aalborgi C1_B.alvinipulli

201050465_B.aalborgi 56-150_B.murdochii

201122867_B.aalborgi

200805639_B.aalborgi

1 200602985_B.aalborgi T.primitia_ZAS-2 201110374d_B.aalborgi o cisil olip.B _ 0 6 6 0 0 8 9 9

201104608_B.aalborgi 201150471_B.aalborgi

201007259_B.aalborgi 200901135_B.aalborgi

200517505_B.pilosicoli 201102752_B.aalborgi

201014350_B.aalborgi

201124639_B.aalborgi o cis olip.B _ 5 6 6 1 3 8 0 0 2 201102362_B.pilosicoli il

200811646_B.aalborgi o cis olip.B _ 0 3 9 9 0 9 0 0 2 il 201104406_B.aalborgi

200808214_B.aalborgi 201024466_B.aalborgi 513A_B.aalborgi o cis olip.B _ 9 3 1 9 0 0 1 0 2 il

WesB_B.pilosicoli o cis olip.B _ 6 6 9 1 0 1 1 0 2 201110374b_B.aalborgi il 201105351g_B.aalborgi

201018213_B.aalborgi

200900639_B.aalborgi

200702703_B.aalborgi

o cis olip.B _ 4 7 3 1 2 2 1 0 2 il 201104149_B.aalborgi 09002 200513182a_B.pilosicoli o cis olip.B _ 8 7 6 0 0 2 1 0 2 il 200513182b_B.pilosicoli

200410620a_B.pilosicoli o cis olip.B _ 1 8 0 2 3 2 0 0 2

200410620b_B.pilosicoli il 200923973_B.aalborgi o cis olip.B _ 6 8 3 5 0 1 1 0 2

il P43/6/78_B.pilosicoli il 200904021_B.aalborgi il ocisolip.B_330907002 igroblaa.B_570307002 o cis olip.B _ 8 2 8 0

ocisolip.B_729402102 201123898_B.aalborgi 201113577_B.aalborgi il 201150177_B.aalborgi o cis olip.B _ 6 5 1 9 0 0 1 0 2 200922746_B.aalborgi il

200707443_B.aalborgi

B256_B.innocens

200917097_B.aalborgi

o cis olip.B _ 0 3 2 5 2 1 1 0 2 200813138b_B.aalborgi

o cis olip.B _ 4 4 9 0 0 3 0 0 2 il

il o cis olip.B _ 5 2 7 4 2 1 1 0 2

o cis olip.B _ 2 9 6 3 1 0 1 0 2

il

il 200805431_B.pilosicoli

o cis olip.B _ k n a B n e G _ 0 0 0 1/5 9

il

0.05

115 201003249_B.aalborgi

igroblaa.B_412808002

igroblaa.B_936009002 201108603_B.hominis

201114303_B.aalborgi 200514702_B.hominis

201202009_B.aalborgi 201024610_B.aalborgi200925995_B.hominis

201129144_B.aalborgi

200902757_B.aalborgi

sinim o h.B _ 3 4 3 8 0 6 0 0 2

igro bla a.B _ 0 5 3 4 1 0 1 0 2 200811646_B.aalborgi sinim o h.B _ 5 6 6 2 0 7 0 0 2 201119045_B.aalborgi sinim o h.B _ 7 0 0 6 1 1 1 0 2

201120460_B.aalborgi 201018213_B.aalborgi 200816817_B.aalborgi 201004769_B.aalborgi

200920244_B.aalborgi 200414761_B.aalborgi

201015580_B.aalborgi 200914805_B.aalborgi 200707443_B.aalborgi

200709653_B.aalborgi 201104406_B.aalborgi 201108681_B.aalborgi

201007259_B.aalborgi 201129345_B.aalborgi

200608126*_B.hominis 200704900_B.aalborgi

200624827_B.aalborgi 201104140_B.hominis 200501138_B.aalborgi 201021258_B.hominis 200113332_B.aalborgi

200803874_B.hominis 201050211_B.aalborgi

201122669_B.aalborgi 201024348_B.hominis 200813138a_B.aalborgi 201003592c_B.hominis 200813138b_B.aalborgi

201003592b_B.hominis 200813138c_B.aalborgi

201003592d_B.hominis 200813138d_B.aalborgi

200813138e_B.aalborgi 200901135_B.aalborgi 200813138g_B.aalborgi 201105351c_B.aalborgi

201022967b_B.aalborgi 200624827_B.aalborgi 201105351b_B.aalborgi 201022967c_B.aalborgi 200430368_B.aalborgi 201105351d_B.aalborgi 201022967d_B.aalborgi

201050465_B.aalborgi 201105351f_B.aalborgi 201022967e_B.aalborgi

201022967f_B.aalborgi 201108681_B.aalborgi 201110374g_B.aalborgi 201022967g_B.aalborgi 201104406_B.aalborgi 200602985_B.aalborgi 201040076_B.aalborgi 201104149_B.aalborgi 201150177_B.aalborgi 200813340_B.aalborgi

201110374a_B.aalborgi 201105351e_B.aalborgi WA1_GenBank_B.hyodysenteriae B-78_B.hyodysenteriae PWS/A_B.intermedia 200923973_B.aalborgi 201001908*_B.aalborgi 200716125_B.aalborgi 513A_B.aalborgi 200914805_B.aalborgi C1_B.alvinipulli B256_B.innocens 201103059_B.aalborgi 200816817_B.aalborgi 200918072_B.aalborgi

200805639_B.aalborgi 56-150_B.murdochii 201129144_B.aalborgi

201105351g_B.aalborgi 201021258_B.hominis 201110374b_B.aalborgi 200922746_B.aalborgi 201024610_B.aalborgi 201110374d_B.aalborgi

201123898_B.aalborgi 200813138c_B.aalborgi 199603205_B.pilosicoli 201150471_B.aalborgi

122102 200702703_B.aalborgi 200805431_B.pilosicoli

200917097_B.aalborgi o cis olip. B _ 4 7 3 il P43/6/78_B.pilosicoli 201104149_B.aalborgi 200513182b_B.pilosicoli

200917337_B.aalborgi o cis olip.B _ 6 5 1 9 0 0 1 0 2 il 200513182a_B.pilosicoli 201023408_B.aalborgi

201111603_B.aalborgi

201104608_B.aalborgi o cis olip.B _ 5 0 5 7 1 5 0 0 2 il

201124639_B.aalborgi 95/1000_GenBank_B.pilosicoli

201110374a_B.aalborgi o cis olip.B _ 1 8 0 2 3 2 0 0 2 200607003_B.hominis il o cis olip.B _ 8 2 8 0 0 9 0 0 2 il 200905511_B.hominis WesB_B.pilosicoli

200410620a_B.pilosicoli o cis olip.B _ 4 4 9 0 0 3 0 0 2

200410620b_B.pilosicoli il 201111933_B.aalborgi o cis olip.B _ 9 3 1 9 0 0 1 0 2 il

200216407_B.aalborgi il 201102362_B.pilosicoli il il

ocisolip.B_039909002

ocisolip.B_669101102

ocisolip.B_527421102 o cis olip.B _ 0 3 2 5 2 1 1 0 2 200913478_B.aalborgi il

200923973_B.aalborgi 200904021_B.aalborgi o cis olip.B _ 2 9 6 3 1 0 1 0 2 il

201024300_B.aalborgi

o cis olip.B _ 8 7 6 0 0 2 1 0 2 201105351a_B.aalborgi201024466_B.aalborgi

o cis olip.B _ 6 8 3 5 0 1 1 0 2 201050465_B.aalborgi o cis olip.B _ 5 6 6 1 3 8 0 0 2 o cis olip.Bil _ 7 2 9 4 0 2 1 0 2 o cis olip.B _ 3 3 0 9 0 7 0 0 2

il il

201122867_B.aalborgi il

il

200430368_B.aalborgi

T.primitia_ZAS-2 0.07

116 igroblaa.B_270819002 201024348_B.hominis

201150177_B.aalborgi

200113332_B.aalborgi

2 00925995_B.hominis 201150471_B.aalborgi

201110374b_B.aalborgi

201122669_B.aalborgi

sinim o h.B _ b 2 9 5 3 0 0 1 0 2 201050211_B.aalborgi sinim o h.B _c2 9 5 3 0 0 1 0 2 sinim o h.B _ d 2 9 5 3 0 0 1 0 2 201109833_B.aalborgi

o cissinim olip.B o h.B _ 6 6_ 1 9 1 1 5 0 5 1 0 1 9 0 0 2 0201113577_B.aalborgi 2

201111933_B.aalborgi il 201104140_B.hominis 513A_B.aalborgi 200501138_B.aalborgi 201114303_B.aalborgi

200920244_B.aalborgi 200902757_B.aalborgi 201001908*_B.aalborgi 200702703_B.aalborgi

201110374d_B.aalborgi 201119045_B.aalborgi

200608343_B.hominis 201111603_B.aalborgi 200901135_B.aalborgi 201003249_B.aalborgi

201105351c_B.aalborgi

200514702_B.hominis 200922746_B.aalborgi

201123898_B.aalborgi 201116007_B.hominis

200707443_B.aalborgi 200702665_B.hominis

200808214_B.aalborgi 200709653_B.aalborgi 201007259_B.aalborgi 200913478_B.aalborgi 201103059_B.aalborgi

200900639_B.aalborgi 200917337_B.aalborgi 201122867_B.aalborgi 201018213_B.aalborgi 200813138g_B.aalborgi 201015580_B.aalborgi i 201022967b_B.aalborgi 200624827_B.aalborgi 200716125_B.aalborgi i 201022967c_B.aalborg 200430368_B.aalborgi 201040076_B.aalborgi 201022967d_B.aalborg lborgi 200414761_B.aalborgi 201050465_B.aalborgi 201022967e_B.aa i 201105351b_B.aalborgi 201022967f_B.aalborg 201108681_B.aalborgi lborgi 201124639_B.aalborgi 201022967g_B.aa 201104406_B.aalborgi i 201105351e_B.aalborgi 201040076_B.aalborg 201104149_B.aalborgi i 201105351a_B.aalborgi 200813340_B.aalborg

201110374a_B.aalborgi 201105351d_B.aalborgi

200923973_B.aalborgi 95/1000_GenBank_B.pilosicoli WesB_B.pilosicolio cisil olip.B _ 3 3 0 9 0 7 0 0 2

200914805_B.aalborgi o cisil olip.B _ 6 8 3 5 0 1 1 0 2 200410620b_B.pilosicolio cis olip.B _ 5 0 2 3 0 6 9 9 1 200410620a_B.pilosicoli il o cisil olip.B _ 5 6 6 1 3 8 0 0 2 200816817_B.aalborgi o cisil olip.B _ 8 7 6 0 0 2 1 0 2 201022967d_B.aalborgi 201022967c_B.aalborgi o cis olip.B _ 2 6 3 2 0 1 1 0 2 200813138e_B.aalborgi il 200813138b_B.aalborgi 200813138d_B.aalborgi

200513182a_B.pilosicoli 201129144_B.aalborgi 200513182b_B.pilosicoli o cis olip.B _ 9 3 1 9 0 0 1 0 2 201022967e_B.aalborgi il o cis olip.B _ 5 0 5 7 1 5 0 0 2 P43/6/78_B.pilosicoli il o cis olip.B _ 5 2 7 4 2 1 1 0 2 il 201021258_B.hominis 200900828_B.pilosicoli o cis olip.B _ 1 3 4 5 0 8 0 0 2 il

201024610_B.aalborgi

o cis olip.B _ 7 2 9 4 0 2 1 0 2 il 200813138c_B.aalborgi

o cis olip.B _ 4 4 9 0 0 3 0 0 2 o cis olip.B _ 4 7 3 1 2 2 1 0 2 il 200704900_B.aalborgi il

sinimo cis o h.B olip.B _ a 2 _ 9 6 5 5 3 1 0 9 0 0 1 0 2 1 0 2 o ciso cis olip.B olip.B _ 0 3 _ 9 1 9 8 0 0 9 2 0 3 0 2 2 0 0 2

o cis olip.B _ 2 9 6 3 1 0 1 0 2 o cis olip.B _ 0 3 2 5 2 1 1 0 2 il il il

il il 201022967h_B.aalborgi

201022967b_B.aalborgi

il

ocisolip.B_066008991

200813138g_B.aalborgi

201014350_B.aalborgi

200813138a_B.aalborgi

200917097_B.aalborgi

201024300_B.aalborgi

200904021_B.aalborgi

200803874_B.hominis

201120460_B.aalborgi

200703075_B.aalborgi

200811646_B.aalborgi

200805639_B.aalborgi 200602985_B.aalborgi

B256_B.innocens

PWS/A_B.intermedia

201104608_B.aalborgi

B-78_B.hyodysenteriae

201202009_B.aalborgi

C1_B.alvinipulli 56-150_B.murdochii

WA1_GenBank_B.hyodysenteriae

0.06 T.primitia_ZAS-2

117 igroblaa.B_670040102

201003592c_B.hominis sinimoh.B_566207002 201104608_B.aalborgi

200901634_B.aalborgi 200813340_B.aalborgi 201103059_B.aalborgi

200905511_B.hominis 201124639_B.aalborgi 201120460_B.aalborgi 201110374b_B.aalborgi 201110374a_B.aalborgi 201110374g_B.aalborgi

sinimoh.B_b295300102

201110374d_B.aalborgi igroblaa.B_646118002 sinimoh.B_a295300102igroblaa.B_344707002

sinimoh.B_d295300102 201007259_B.aalborgi 201014350_B.aalborgi 200703075_B.aalborgi 200808214_B.aalborgi sinimoh.B_e295300102 201111603_B.aalborgi 201108603_B.hominis 200101917_B.aalborgi 201024348_B.hominis 200902757_B.aalborgi 201024610_B.aalborgi 201022967i_B.aalborgi 201023408_B.aalborgi 201022967g_B.aalborgi 201129144_B.aalborgi 201022967h_B.aalborgi 513A_B.aalborgi 201022967e_B.aalborgi 201122867_B.aalborgi 201022967f_B.aalborgi 201022967c_B.aalborgi 200702703_B.aalborgi 201022967d_B.aalborgi 200917097_B.aalborgi 200624827_B.aalborgi 200918072_B.aalborgi 200704900_B.aalborgi 200813138g_B.aalborgi 200813138h_B.aalborgi 200904021_B.aalborgi 200813138e_B.aalborgi 201003249_B.aalborgi 200813138f_B.aalborgi 200813138c_B.aalborgi 200514702_B.hominis 200813138d_B.aalborgi 200813138a_B.aalborgi 200608343_B.hominis 200813138b_B.aalborgi 200414761_B.aalborgi 200709653_B.aalborgi

200501138_B.aalborgi 200805639_B.aalborgi 200813138b_B.aalborgi 201114303_B.aalborgi 200602985_B.aalborgi 200607003_B.hominis 201110374b_B.aalborgi 200803874_B.hominis 201102752_B.aalborgi 95/1000_GenBank_B.pilosicoli 200925995_B.hominis 201104149_B.aalborgi 201001908*_B.aalborgi 200113332_B.aalborgi 200608126*_B.hominis

201021258_B.hominis WA1_GenBank_B.hyodysenteriae P43/ 56-150__B.murdochii 6/78_B.pilosicoli B-78_B.hyodysenteriae 201004769_B.aalborgi B256_B.innocens PWS/A_B.intermedia 21102 ilocisolip.B_5274

201050211_B.aalborgi

ol ip.B_032521102 C1_B.alvinipulli ilocis

201024300_B.aalborgi ol ip.B_683501102

201104406_B.aalborgi ilocis ol ip.B_729402102

201050465_B.aalborgi ilocis

so l i p .B_473122102 201119045_B.aalborgi iloci

201116007_B.hominis

cisol ip.B_039909002 ilocisolip.B_066008991 ilo

201150471_B.aalborgi ilocisolip.B_527421102 200703075_B.aalborgi 201150177_B.aalborgi ilocisolip.B_729402102

201015580_B.aalborgi ilocisolip.B_502306991 ilocisolip.B_330907002 B_876002102 201202009_B.aalborgi ilocisolip.B_566138002 200900639_B.aalborgi ilocisolip. 200914805_B.aalborgi 200513182b_B.pilosicoli ilocisolip.B_039909002 200513182a_B.pilosicoli 200917337_B.aalborgi ilocisolip.B_473122102 200410620b_B.pilosicoli 200901135_B.aalborgi 200410620a_B.pilosicoli ilocisolip.B_683501102 201104140_B.hominis ilocisolip.B_180232002 200816817_B.aalborgi

P43/6/78_B.pilosicoli ilocisolip.B_651900102 201018213_B.aalborgi WesB_B.pilosicoli 95/1000_GenBank_B.pilosicoli

201024466_B.aalborgi ilocisolip.B_828009002 201111933_B.aalborgi

igroblaa.B_e153501102 200923973_B.aalborgi igroblaa.B_d153501102 200913478_B.aalborgi 201122669_B.aalborgi ilocisolip.B_263201102 201108681_B.aalborgi 200716125_B.aalborgi 201113577_B.aalborgi ilocisolip.B_449003002 200920244_B.aalborgi ilocisolip.B_931900102 200430368_B.aalborgi ilocisolip.B_505715002 201129345_B.aalborgi ilocisolip.B_669101102 201109833_B.aalborgi ilocisolip.B_032521102

201105351a_B.aalborgi200922746_B.aalborgi ilocisolip.B_296310102 201123898_B.aalborgi

ilocisolip.B_134508002

201105351c_B.aalborgi

201105351b_B.aalborgi

igroblaa.B_f153501102

0.07

2-SAZ_ai rp.T imi t

118

201119045_B.aalborgi 201150177_B.aalborgi

201015580_B.aalborgi 201050465_B.aalborgi 201104140_B.hominis 201021258_B.hominis

200920244_B.aalborgi

200925995_B.hominis

201111933_B.aalborgi 201004769_B.aalborgi

201102752_B.aalborgi 200624827_B.aalborgi 201109833_B.aalborgi 201122867_B.aalborgi

200602985_B.aalborgi

200803874_B.hominis 200608126*_B.hominis 200922746_B.aalborgi

200918072_B.aalborgi

200805639_B.aalborgi 200704900_B.aalborgi

201123898_B.aalborgi 200702703_B.aalborgi 201003249_B.aalborgi 201024348_B.hominis

201007259_B.aalborgi 200904021_B.aalborgi 200808214_B.aalborgi 200608343_B.hominis

201003592a_B.hominis 200514702_B.hominis 200501138_B.aalborgi

201014350_B.aalborgi 200414761_B.aalborgi

201003592c_B.hominis 200113332_B.aalborgi

201003592b_B.hominis 201024300_B.aalborgi

201104608_B.aalborgi 201050211_B.aalborgi

201003592d_B.hominis 201104406_B.aalborgi

200905511_B.hominis 201116007_B.hominis

200901634_B.aalborgi 201202009_B.aalborgi

200716125_B.aalborgi 200914805_B.aalborgi

200917337_B.aalborgi 200900639_B.aalborgi

201104149_B.aalborgi 200816817_B.aalborgi 201110374g_B.aalborgi 201018213_B.aalborgi

200917097_B.aalborgi 200913478_B.aalborgi

200813138b_B.aalborgi 200923973_B.aalborgi

201110374b_B.aalborgi 201108681_B.aalborgi

95/1000_GenBank_B.pilosicoli

201122669_B.aalborgi

B256_B.innocens 201113577_B.aalborgi

P43/6/78_B.pilosicoli 201129345_B.aalborgi

o cisil olip.B _ 5 2 7 4 2 1 1 0 2 2 0 0 6 0 7 0 0 3 _ h.B o sinim

i lpB_032521102 0 1 1 2 5 2 3 0 _ olip.B cis o

il igro bla a.B _ 3 5 6 9 0 7 0 0 2

i lpB_683501102 0 1 1 0 5 3 8 6 _ olip.B cis o il igro bla a.B _ a 8 3 1 3 1 8 0 0 2

200813138c_B.aalborgi

i lpB_729402102 0 1 2 0 4 9 2 7 _ olip.B cis o il

200813138d_B.aalborgi i lpB_473122102 0 1 2 2 1 3 7 4 _ olip.B cis o

il 200813138e_B.aalborgi

solioci i lpB_039909002 0 0 9 0 9 9 3 0 _ olip.B cis o

il il

200703075_B.aalborgi PWS/A_B.intermedia B-78_B.hyodysenteriae il WA1_GenBank_B.hyodysenteriae

200813138g_B.aalborgi igro bla a.B _f8 3 1 3 1 8 0 0 2 201024466_B.aalborgi

201022967b_B.aalborgi

201022967c_B.aalborgi

i lpB_296310102 0 1 0 1 3 6 9 2 _ olip.B cis o

il 201022967d_B.aalborgi

. _134508002 p.B 201022967e_B.aalborgi

ocisoli il

201022967f_B.aalborgi

ciso olip.B _ 5 0 5 7 1 5 0 0 2

il 201022967g_B.aalborgi

o cis olip.B _ 6 6 9 1 0 1 1 0 2 201022967h_B.aalborgi il

201022967i_B.aalborgi

200410620b_B.pilosicoli

o cis olip.B _ 4 4 9 0 0 3 0 0 2 C1_B.alvinipulli

il 56-150_B.murdochii

201023408_B.aalborgi

200410620a_B.pilosicoli

o cis olip.B _ 9 3 1 9 0 0 1 0 2 201024610_B.aalborgi il

201105351b_B.aalborgi

201105351c_B.aalborgi

201105351d_B.aalborgi 200513182b_B.pilosicoli

201105351g_B.aalborgi

200513182a_B.pilosicoli

o cis olip.B _ 2 6 3 2 0 1 1 0 2 il 201111603_B.aalborgi

201114303_B.aalborgi

o cis olip.B _ 3 3 0 9 0 7 0 0 2

il 200101917_B.aalborgi 08991

200702665_B.hominis

200232081_B.pilosicoli 200707443_B.aalborgi

200811646_B.aalborgi

200813340_B.aalborgi

201103059_B.aalborgi

201124639_B.aalborgi

o cis olip.B _ 0 6 6 0 200902757_B.aalborgi

201200678_B.pilosicoli 201108603_B.hominis

il 201129144_B.aalborgi

513A_B.aalborgi

o cis olip.B _ 8 2 8 0 0 9 0 0 2

il

WesB_B.pilosicoli

o cis olip.B _ 6 5 1 9 0 0 1 0 2

200901135_B.aalborgi

il

201150471_B.aalborgi o cis olip.B _ 5 6 6 1 3 8 0 0 2

il

201110374d_B.aalborgi T.primitia_ZAS-2

0.05

119 201022967g_B.aalborgi

201022967d_B.aalborgi

igroblaa.B_804320102 201022967c_B.aalborgi

201022967b_B.aalborgi sinimoh.B_843420102

200917097_B.aalborgi 200813138g_B.aa

200813138e_B.aalborgi

200813138d_B.aalborgi

200813138c_B.aalborgi

200813138b_B.aalborgi

200813138a_B.aalborgi

200805639_B.aalborgi

igroblaa.B_f769220102 lborgi igroblaa.B_e769220102

201024610_B.aalborgi 200709653_B.aalborgi 201105351b_B.aalborgi 201105351c_B.aalborgi

201105351d_B.aalborgi

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200607003_B.hominis 201105351f_B.aalborgi

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201003592d_B.hominis 200923973_B.aalborgi 201104608_B.aalborgi 200811646_B.aalborgi 200813340_B.aalborgi

200913478_B.aalborgi 200905511_B.hominis

201103059_B.aalborgi 201018213_B.aalborgi 201024300_B.aalborgi 201120460_B.aalborgi 201111933_B.aalborgi 201124639_B.aalborgi

201104140_B.hominis 201110374g_B.aalborgi 200925995_B.hominis 200816817_B.aalborgi 200902757_B.aalborgi 200113332_B.aalborgi 200216407_B.aalborgi 200917337_B.aalborgi 200414761_B.aalborgi 201108603_B.hominis 200901135_B.aalborgi 201129144_B.aalborgi 200514702_B.hominis 200900639_B.aalborgi 513A_B.aalborgi 200608343_B.hominis 200914805_B.aalborgi 200918072_B.aalborgi 56-150_B.murdochii B256_B.innocens 200803874_B.hominis 201015580_B.aalborgi PWS/A_B.intermedia 200904021_B.aalborgi WA1_GenBank_B.hyodysenteriae 201202009_B.aalborgi B-78_B.hyodysenteriae 201003249_B.aalborgi 200716125_B.aalborgi 201150471_B.aalborgi C1_B.alvinipulli 200704900_B.aalborgi 201150177_B.aalborgi 201122867_B.aalborgi 201119045_B.aalborgi 201110374b_B.aalborgi

201116007_B.hominis 201110374d_B.aalborgi 200901135_B.aalborgi 199603205_B.pilosicoli 201104406_B.aalborgi

201050211_B.aalborgi 201200678_B.pilosicoli

201024300_B.aalborgi

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200414761_B.aalborgi 200410620b_B.pilosicoli ilocisolip.B_180232002 200410620a_B.pilosicoli

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201003249_B.aalborgi

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ilocisolip.B_BseW ilocisolip.B_931900102 200624827_B.aalborgi ilocisolip.B_505715002 201105351a_B.aalborgi201024466_B.aalborgi ilocisolip.B_669101102 200704900_B.aalborgi ilocisolip.B_032521102 201050465_B.aalborgi ilocisolip.B_527421102

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0.07

T.primitia_ZAS-2

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201104149_B.aalborgi

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200920244_B.aalborgi

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200923973_B.aalborgi igro bla a.B _ g 8 3 1 3 1 8 0 0 2

201022967h_B.aalborgi

201024610_B.aalborgi 201111933_B.aalborgi 201105351a_B.aalborgi 201105351b_B.aalborgi 201105351d_B.aalborgi 201104140_B.hominis 201105351e_B.aalborgi 200816817_B.aalborgi 201111603_B.aalborgi 201114303_B.aalborgi 200917337_B.aalborgi 200808214_B.aalborgi 201007259_B.aalborgi 200914805_B.aalborgi 201014350_B.aalborgi 201040076_B.aalborgi 201015580_B.aalborgi 200702665_B.hominis 201150471_B.aalborgi 200707443_B.aalborgi 200811646_B.aalborgi 201150177_B.aalborgi 201003592b_B.hominis 201119045_B.aalborgi 201003592c_B.hominis 201003592d_B.hominis 201116007_B.hominis 200905511_B.hominis 201104406_B.aalborgi 201103059_B.aalborgi

201050465_B.aalborgi 201124639_B.aalborgi

i 201110374a_B.aalborgi 201024300_B.aalborgi 201120460_B.aalborgi 201110374b_B.aalborgi i 201124639_B.aalborg 201021258_B.hominis 201110374d_B.aalborgi 201110374g_B.aalborg i 200925995_B.hominis 200902757_B.aalborgi 200902757_B.aalborg i 201129144_B.aalborgi 200113332_B.aalborgi 200216407_B.aalborg 513A_B.aalborgi s 200414761_B.aalborgi ocisolip.B_669101102il 201108603_B.homini i 201129144_B.aalborg 200514702_B.hominis WA1_GenBank_B.hyodysenteriae B-78_B.hyodysenteriae 513A_B.aalborgi PWS/A_B.intermedia 200608343_B.hominis 56-150_B.murdochii 200803874_B.hominis B256_B.innocens

200904021_B.aalborgi C1_B.alvinipulli

201003249_B.aalborgi 200909930_B.pilosicoli 200704900_B.aalborgi 2002

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0.06

T.primitia_ZAS-2

121

122

123 124 444 A

4

Chapter 6

Abstract

126

chapter 5

127 Chapter 6

Materials and methods

Brachyspira pilosicoli

128

chapter 5

Sequence analysis

atpG

129 Chapter 6

Results Biopsy samples

aptG

130 Table 1:

Sample ID Country of origin County Host Type of sample ST

Human Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

131 Table 1:

Sample ID Country of origin County Host Type of sample ST

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human

Human Human

132 WA1 B-78 PWS/A 513A 56-150 C1 T.primitia_ZAS-2 T1 @ 199800660 @ 200517505 @ WesB @ K1 @ 201101966 @ 201009139 @ 201102362 @ 200909930 @ 200831665 @ HRM_4B @ HRM_2B @ N1 @ RV1 @ SC1 @ 7072i @ 201013692 @ 200300944 @ 200410620a @ 200410620b @ 200709033 @ 200513182a @ 200513182b @ 200900828 @ 201009156 @ 200232081 @ 201105386 @ 201204927 @ 201221374 @ 201200678 @ f199600014 @ HRM7A @ HRM7 @ H60-2 @ H38-2 @ H4-2 @ J_F2 @ QF1 @ EM1 @ M1 @ V1_H141 @ @: Human B256 201124725 @ 201125230 @ 200805431 @ V1_H11 @ H21 @

0.05 Figure 1:

133 WA1 B-78 PWS/A 56-150 B256 C1 T.primitia_ZAS-2 513A 201101966 @ T1 A WesB @ B K1 @ 200909930 @ HRM_4B @ HRM_2B @ HRM7A @ HRM7 @ N1 @ RV1 @ SC1 @ 200517505 @ 200300944 @ 201204927 @ 7072i @ 201124725 @ 201105386 @ 200513182a @ 200513182b @ EM1 @ 200232081 @ 201009156 @ V1_H141 @ 201221374 @ V1_H11 @ QF1 @ 201125230 @ 201013692 @ 200900828 @ 200410620a @ 200410620b @ 201200678 @ 200805431 @ H60-2 @ C M1 @ 201009139 @ 200709033 @ 201102362 @ 200831665 @ JF2 @ H21 @ @: Human Q98.0028.3 H38-2 @ H4-2 @ 0.05 Figure 2:

134 Table 2:

MLST Length Locus alleles (bp) sites

44

atpG

Human Chicken Pig Dog

Figure 3:

135 The Netherlands Italy United Kingdom Australia Papua New Guinea United States of America

Figure 4:

136

Discussion

137 Chapter 6

138

139 Chapter 6

140

References 2 64 7 65 4 31 J 22 J 31 51 40 146 141 63 12 106 29 153 95 2 J 24 23 27 119 12 28 53 23 35 13 21 In Press. 33

141 Chapter 6

13

142 143 144 A4 4

4

Chapter 7

Abstract

146 VSH-1 in Brachyspira Aalborgi

In

4 In .

147 Chapter 7

Materials and methods Ethics statement

Analysis of genomic sequence

Primer design 4

148 VSH-1 in Brachyspira Aalborgi

Table 1:

Presence of svp38 Species

®

149 Chapter 7

Sequencing

150 VSH-1 in Brachyspira Aalborgi

Results Analysis of genome sequence .

Table 2:

Primer name Sequence Set

151 Chapter 7

152 Hvp 38 VSH-1 associated protein B. intermedia PWS/A (GenBank) B. intermedia PWS/A B. alvinipulli C1 Cluster A1 B. hyodysenteriae WA1 (GenBank) B. hyodysenteriae B-78 Cluster A B. intermedia HB60 (GenBank) B. murdochii 56-150 (GenBank) B. murdochii 56-150 Cluster A2 B. innocens B256 T57 (B. aalborgi) U14 (B. aalborgi) U70 (B. aalborgi) 23 (B. aalborgi) 125 (B. aalborgi) 192 (B. aalborgi) 258 (B. aalborgi) Cluster B1 259 (B. aalborgi) 261 (B. aalborgi) 263 (B. aalborgi) 266 (B. aalborgi) 39 (B. aalborgi) B. pilosicoli P43/6/78 (GenBank) B. pilosicoli P43/6/78 U32 (B. pilosicoli) U49 (B. pilosicoli) U38 (B. aalborgi) 243 (B. pilosicoli) L09 (B. aalborgi) V01a (B. pilosicoli) 153 (B. pilosicoli) Cluster B 154 (B. pilosicoli) 95 (B. aalborgi) 225 (B. pilosicoli) 8 (B. aalborgi) 175 (B. aalborgi) Cluster B2 0. 01 B. pilosicoli WesB (GenBank) U22 (B. aalborgi) T24 (B. pilosicoli) 150 (B. pilosicoli) 85 (B. aalborgi) 140 (B. aalborgi) B. pilosicoli B2904 (GenBank) B. pilosicoli 95/1000 (GenBank) B. pilosicoli WesB 37 (B. aalborgi) 75 (B. aalborgi) 128 (B. aalborgi) 256 (B. aalborgi) 257 (B. aalborgi)

Figure 1:

153 Chapter 7

Discussion

154 VSH-1 in Brachyspira Aalborgi

155 Chapter 7

156 VSH-1 in Brachyspira Aalborgi

157 Chapter 7

References 134 27 12 187 23 179 13 224 13 12 31 74 132 134 38 2 3 59 52 39 J 16 68 29 41 4 67 51 95 7

158 159 160 4A

4

Chapter 8

Abstract

Design

Results p pp p

Conclusion

162 Epidemiology of HIS in the Netherlands

Figure 1:

163 Chapter 8

Methods Ethics statement

164 Epidemiology of HIS in the Netherlands

January 1991 for presence of HIS December 2011

Search term ‘colon + biopsy’ HIS not present 20% randomly selected as controls All colon-biopsies n = 1,205,676 50.28% females 49.82% males

HIS-cases Controls Search term n = 1,243 n = 351 ‘’ 28.96% females 60.32% females (+ related spellings) 71.04% males 39.68% males

n = 3,003 Requested from 47.25% females pathology laboratories 52.75% males

Figure 2:

as

165 Chapter 8

p

166 Epidemiology of HIS in the Netherlands

Results

p p

p

167 pathology laboratories

HIS-cases Controls

for processing n = 5

PCR Brachyspira

n = 631 n = 100

Internal control

n = 78 n = 22

PCR

n = 33 n = 45

Exclusion Inclusion

HIS-cases Controls Figure 3:

168 Table 1:

Complaint without Complaint with B. Complaint Complaint present p B. pilosicoli pilosicoli

4

Table 2:

n Diagnosis

44

169 Chapter 8

pp

170 Groningen SIR biopsies: 0.89 (0.88 - 0.90) SIR HIS: 0.29 (0.13 - 0.55) Pigs 63.7/km2 Poultry 2.376.6/km2 HIV-centres 1/30

Noord-Holland SIR biopsies: 1.01 (1.01 - 1.02) SIR HIS: 1.84 (1.63 - 2.08) Pigs 9.7/km2 2 Poultry 493.4/km Friesland HIV-centres 9/30 SIR biopsies: 1.04 (1.02 - 1.05) SIR HIS: 0.21 (0.08 - 0.42) Pigs 31.8/km2 Poultry 2,187.2/km2 Drenthe HIV-centres 1/30 SIR biopsies: 0.92 (0.90 - 0.93) Flevoland SIR HIS: 0.54 (0.29 - 0.90) SIR biopsies: 1.20 (1.18 - 1.22) Pigs 107,5/km2 SIR HIS: 2.24 (1.62 - 3.02) Poultry 2,363.8/km2 Pigs 40.8/km2 HIV-centres 0/30 Poultry 1,461.9/km2 Overijssel HIV-centres 2/30 SIR biopsies: 0.94 (0.93 - 0.95) SIR HIS: 0.96 (0.72 - 1.24) Pigs 483.2/km2 Poultry 2,943.3/km2 HIV-centres 2/30 Utrecht SIR biopsies: 0.97 (0.96 - 0.98) SIR HIS: 0.93 (0.71 - 1.20) Pigs 219.1/km2 Poultry 1,227.9/km2 HIV-centres 2/30 Gelderland SIR biopsies: 1.08 (1.08 - 1.09) SIR HIS: 0.48 (0.36 - 0.64) Pigs 442.9/km2 Zuid-Holland 2 SIR biopsies: 0.99 (0.98 - 0.99) Poultry 3,439.3/km SIR HIS: 0.46 (0.37 - 0.57) HIV-centres 2/30 Pigs 56.5/km2 Poultry 390.0/km2 HIV-centres 7/30

Noord-Brabant SIR biopsies: 0.82 (0.81 - 0.82) SIR HIS: 0.58 (0.46 - 0.73) Limburg Pigs 1,078.6/km2 SIR biopsies: 1.27 (1.26 - 1.28) 2 SIR HIS: 2.92 (2.51 - 3.38) Poultry 5,330.5/km 2 HIV-centres 2/30 Pigs 790.6/km Poultry 6,880.0/km2 HIV-centres 1/30

Zeeland SIR biopsies: 0.86 (0.85 - 0.88) SIR HIS: 1.03 (0.64 - 1.58) Pigs 43.6/km2 Poultry 1,015.2/km2 HIV-centres 1/30

Figure 4:

171 150000 200

150 100000

100

50000 HIS Biopsies 50

0 0

199119921993199419951996199719981999200020012002200320042005200620072008200920102011 Year Figure 5:

1 Appendix (3.7%) 4 2 Coecum (13.2%) 3 Ascending colon (10.9%) 4 Transversing colon (7.8%) 5 Descending colon (10.1%) 3 6 Sigmoid (13.0%) 5 7 Rectum (10.4%)

2 1 6 7

Figure 6:

172 4 4

3 3 A 5 C 5 2 1 2 1 6 6 7 7

4 4

3 3 B 5 D 5 2 1 2 1 6 6 7 7

Figure 7:

Table 3:

B. pilosicoli B. pilosicoli p (n = 150) absent present

B. pilosicoli B. pilosicoli p (n = 126) absent present

173 Chapter 8

Discussion

4

174 Epidemiology of HIS in the Netherlands

175 Chapter 8

176 Epidemiology of HIS in the Netherlands

177 Chapter 8

References 95 16 3 2 82 2 7 Int J 4 18 J 22 21 45 101 63 85 62 27 106 59 146 21 51 53 59 132 39 70 82 29 22

178 Epidemiology of HIS in the Netherlands

39 31 31 J 31 40 141 12 41 303 42 32

179 180 182 Discussion

Aim of this thesis

Pathogenicity chapter 4

chapters 2 8 As chapter 4 chapter 8 chapters 2 8 .

183 A

B

Figure 1:

184 Discussion

.

185 Chapter 9

(chapter 2

chapter 1 chapter 1 chapter 1

186 Discussion

Chapter 5

atpG chapter 7

187 Chapter 9

Epidemiology chapter 1 chapter 6

chapter 8

188 Discussion

chapters 4 8chapter 4 chapter 8 chapter 4

Chapter 8 p chapter 3

Zoonosis chapter 5chapter 6

189 B`åckhäns et al. EnvironB`åckhäns Rep, Microbiol 2010. 2(6): p. 720-7. ‘Brachyspira muridarum’ ‘Brachyspira rattus’ ‘Brachyspira muris’ 2010 Chander et al. J Vet Invest, Diagn 2012. 24(5): p. 903-10. ‘Brachyspira hampsonii’ Jansson et al. Anaerobe, 2008. 14(5): p. 287-95. ‘Brachyspira corvi’ 2012 2008 ‘Brachyspira suanatina’ Råsbäck et al. EnvironRåsbäck Microbiol, 2007. 9(4): p. 983-91. 2007 ‘Spirochaeta steonogyrata’ ‘Spirochaeta eurygyrata’ Werner. Centralbl. f. Bakt. Orig., 1909. 1(lii): p. 241-3. 1909 ‘Borrelia eurygyrata’ Harland et al.Harland BMJ, 1967. 3(5567): p. 718-9. 1967 Hovind-Hougen et al. JCM, 1982. 16(6): p. 1127-36. Brachyspira aalborgi 1982 Stephens et al. Avian Pathol, 1999. 28(5): p. 447. ‘Brachyspira pulli’ 1999 B. hyodysenteriae B. intermedia B. murdochii B. alvinipulli B. innocens Brachyspiraceae B. pilosicoli B. aalborgi Treponema hyodysenteriae Harris et al.Harris Vet Small Anim Clin, 1972. 160(4): p. Med 561-5. 2013 1972 'B. muridarum' 'B. hampsonii' 'B. suanatina' 'B. rattus' 'B. muris' 'B. canis' 'B. corvi' Brachyspira hyodysenteriae 'B. pulli' Ochiai et al.Ochiai Immunol, 1997. 41(6): p. Microbiol 445-52. Brachyspira innocens Brachyspira pilosicoli Duhamel et al.Duhamel J Clin Microbiol, 1998. 36(8): p. 2264-70. ‘Brachyspira canis’ 1997 Serpulina hyodysenteriaeSerpulina 1998 Stanton J Syst Int 1992. 42(1): p. Bacteriol, 189-90. Serpulina innocens Serpulina Serpula hyodysenteriaeSerpula Stanton et al. J Syst Int 1991. 41(1): p. Bacteriol, 50-8. Serpula innocens Serpula 1992 1991 Kinyon et al. J Syst Int 1979. 29(2): p. Bacteriol, 102-9. Treponema innocens Hampson et al. J Syst Int Evol Microbiol, 2006. 56(5): p. 1009-12. 1979 Brachyspira intermedia Brachyspira murdochii Brachyspira alvinipulli Stanton et al. J Syst Int 1998. 48(3): p. Bacteriol, 669-76. Brachyspira alvinipulli Trott et al. J Syst Int 1996. 46(1): p. Bacteriol, 206-15. Serpulina pilosicoli Serpulina 2006 1998 1996 Lee et al. Vet Microbiol, 1993. 34(3): p. 273-85. ‘Anguilina coli’ 1993 2: Figure Stanton et al. J Syst Int 1997. 47(4): p. Bacteriol, 1007-12. Serpulina intermedia Serpulina Stanton et al. J Syst Int 1997. 47(4): p. Bacteriol, 1007-12. Serpulina murdochii Serpulina 1997 1997

190 Discussion

4 chapters 5 6 44

Conclusion

191 Chapter 9

References 45 3 2 39 51 4 23 J 22 141 45 8 303 67 121 27 53 16 2 86 37 J 38 38 165 74 160 224 67 134

192 Discussion

47 111 9 24 119 21 63 33 64 65 32 48 13

193 194 A 196

en met

en

197 Addendum

met en

In

198

In .

tussen en

199 Addendum

In

200

. en .

201 202 Dankwoord

203 Addendum

204 Dankwoord

205 Addendum

206 Dankwoord

207