next generation phylogenetics phylogenetics of pathogenic
TRANSCRIPT
5/15/2017
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Translational Genomics Research Institute | www.tgennorth.org
David M. Engelthaler, PhD
Associate Professor
Director, TGen North
Translational Genomics Research Institute
Phylogenetics of
Pathogenic Environmental Fungi
Translational Genomics Research Institute | www.tgennorth.org
Next GenerationPhylogenetics
• Advances in sequencing technology allow for:
– Complete survey of genome phylogenetic markers
• SNPs, indels, genes, CNVs, LGT, etc
– Rapid and relatively inexpensive WGS allows for dozens to hundreds of genomes
– Use of multiple tools for phylogenetic understanding
• Pop structure, hybridization/introgression, recombination, incomplete lineage sorting, etc
Translational Genomics Research Institute | www.tgennorth.org
From Genotyping to Phylotyping
• Genotyping: Linkage of isolates based on genetic similarity
– MicroSats, MLST, AFLP, RFLP, etc.
• Phylotyping: Linkage of isolates based on evolutionary relationships
– Whole Genome SNP Typing, wgMLST, cgMLST
– needs context: whole genomes and entire populations
Translational Genomics Research Institute | www.tgennorth.org
Phylogenetics Applied
• Ancient Dispersal and Emerging Fungi
• Previously unseen and unexplored environmental fungi
• Transplant Outbreaks
• Healthcare product contamination
Population GenomicsGenomic Epidemiology
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Coccidioides
Cryptococcus
ApophysomycesExserohilum
FungalPlayers
Sarocladium
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Coccidioides posadasii and C. immitis
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Global DistributionCoccidioides sp. grows in the soil in arid, hot areas
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Coccidioides phylogeny from microsatellite analysis
Fisher et al, PNAS 2002 8
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Translational Genomics Research Institute | www.tgennorth.orgposterior
1
0.25
0.01.02.03.04.05.06.0
SJV_6
730332_Guatemala
Tucson_17Tucson_22
SJV_8
730334_Guatemala
Nuevo_Leon_2
Phoenix_2
B0858_Guatemala
Tucson_18
Tucson_8
Tucson_15
Michoacan_1
730333_Guatemala
Washington_1
San_Antonio_1
SJV_9
Coahuila_2
GT017_ParaguayB10813_Texas
SJV_7
Tucson_11
SJV_4
Sonora_2
Phoenix_4
Phoenix_5
Tucson_6
Tucson_7
Michoacan_2
Tucson_2
Tucson_16
Tucson_10
Tucson_19
Nuevo_Leon_1
Tucson_1
Tucson_24
SJV_11
GT002_Texas
WA221_Washington_soil
Tucson_9
SJV_10
SJV_1
B0727_Argentina
B5773_Brazil
Colorado_Springs_1
San_Diego_1
Tucson_3
Phoenix_3
SJV_2
SJV_3
Tucson_13
B10757_NevadaTucson_14
Tucson_20
Phoenix_6
Tucson_23
Tucson_12
Tucson_21
B1249_Guatemala
Phoenix_7
Guerrero_1
Tucson_4
Phoenix_1
Phoenix_8
Tucson_5
Sonora_1
Phoenix_9
Coahuila_1
SJV_5
MYA
C. immitis
C. posadasii
BEAST: GTR + GStrict Constant
405,244 total SNPs
Whole Genome SNP Phylogeny
(n=70)
Engelthaler et al mBio 2016
Translational Genomics Research Institute | www.tgennorth.org
C. posadasiiWhole GenomeSNP PhylogenyBEAST
Engelthaler et al mBio 2016
Translational Genomics Research Institute | www.tgennorth.org
Fixed K=3
C. posadasiiAdmixture results of BAPS population structure analysis:
Best population structure:K=3
Admixture
Arizona
Guatemala
Tex-Mex-SA
Engelthaler et al mBio 2016
Translational Genomics Research Institute | www.tgennorth.org
FinestructureC.p. and C.i.
Engelthaler et al mBio 2016
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Translational Genomics Research Institute | www.tgennorth.org
800 kya 600 400 200 Present
GABI 3 GABI 4
Drain of Cen CA Basin
Central Am.South Am.Tex-MexCentral AZSouth AZ-Sonora
Central CA ValleySouth CA-Baja MxSE Washington
Geo-spatial PhylogeneticsThe Dispersal of Coccidioides
Engelthaler et al mBio 2016
Translational Genomics Research Institute | www.tgennorth.org
The Washington Cocci Cases
A new endemic zone?
Translational Genomics Research Institute | www.tgennorth.org
Field Investigation:Coccidioides identified in soil
2010: soil was collected from two locations in SE WA where patients reported potential exposures
No reliable test for identifying Coccidioides in soil existed at the time
▪ 2013: a novel, real-time PCR assay develop
▪ Detected DNA in 6/22 soil samples
• CDC improved ability to isolate from soil
• C. immitis isolated from 4/6 positive samples
Marsden-Haug et al, MMWR 2014Litvintseva, et al CID 2015
Coccidioides identified WA Patients, 2010
Translational Genomics Research Institute | www.tgennorth.org
Whole Genome SNP Typing of C. immitis isolates
Clinical isolate was genetically indistinguishable from environmental isolates
Litvintseva et al. CID 2015
Case
Soil
Soil
Soil
Soil
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Translational Genomics Research Institute | www.tgennorth.org
CDC202_soil
Washington_1
WA221_Washington_soil
CDC212_soil
CDC211_soil
CDC205_soil
3000048581_CDC
3000050036_WA
San_Joaquin_Valley_2
San_Joaquin_Valley_9
San_Joaquin_Valley_11
San_Joaquin_Valley_5
San_Joaquin_Valley_6
San_Diego_1_ref
3000373807_WA
6194
209
6255
115
9464
7037
6513
7374
6543
1
0
2
2
0
3
1524
2001
2595
1946
2061
795
6652
39
159
2000
The Washington Clone
Patient
Patient
Patient
Translational Genomics Research Institute | www.tgennorth.org
CDC202_soil
Washington_1
WA221_Washington_soil
CDC212_soil
CDC211_soil
CDC205_soil
3000048581_CDC
3000050036_WA
1
3
0
2
2
0
115
209
159
39
5 0
The Washington “Clone”
Patient
Patient
Patient
Translational Genomics Research Institute | www.tgennorth.org
Cryptococcus gattiiin Pacific Northwest
Translational Genomics Research Institute | www.tgennorth.org
Cryptococcus gattiiin Pacific Northwest
• Emerged on Vancouver Island in 1999 (VGIIa)
• 2nd outbreak US: human cases in Oregon and Washington (VGIIc)
• Peripatric Black Swan Events
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Translational Genomics Research Institute | www.tgennorth.org
Molecular divergence between the major haploid molecular types of the Cryptococcus species complex
18.5
37
9.5
C. neoformans var. grubii
C. n. var. neoformans
C. gattii
24.5
49
12.5
4.5
8.5
11.7
VNI
VNII
VNIV
VGI
VGIII
VGIV
VGII
A
D
B
C ACT1, IDE, PLB1, URA5mtRNA, ITS1/2, OMP, DOX
Molecular Ecology 2000, Vol 9(10) 1471-1481
Multiple gene genealogies reveal recent dispersion and hybridization in the human pathogenic fungus Cryptococcus neoformans
Jianping Xu1,2,*, Rytas Vilgalys2, Thomas G. Mitchell1
Translational Genomics Research Institute | www.tgennorth.org
80000.0
WM_3032_Australia_Clinical_VGII
WM
_08_309_Australia_V
eterinary_VG
II
CD
C_
32
43
WM
_1
1_
13
9_
VG
III
B2_
Bra
zil_
Anim
al_V
GII
WM_05_530_Brazil_Clinical_VGII
WM
_05_525_B
razil_
Clin
ical_
VG
II
B9764_WA_cat_VGII
WM
_0
5_
52
7_
Bra
zil_
Clinic
al_
VG
II
B8
825
_O
R_
hum
an_
VG
IIc
A5_Brazil_Environmental_VGII
WM
_11_941_V
GIII
WM
_05_547_Brazil_C
linical_VG
II
WM
_0
5_
46
2_
Bra
zil_
Clin
ica
l_V
GII
WM_179_VGI
WM
_05_456_B
razil_
Enviro
nm
enta
l_V
GII
WM
_1846_VGIII
WM_04_78_Colombia_Clinical_VGII
WM
_182
6_V
GIII
WM_11_32_VGIII
R265
WM_779_VGIV
B9563_WA_porpoise_VGIIb
WM
_11_
950_V
GIII
WM
_0
5_
45
2_
Bra
zil_
Clin
ica
l_V
GII
WM_05_528_Brazil_Clinical_VGII
CDC_3225
WM_1802_VGIII
B11_Greece_Human_VGII
WM
_1
85
1_
Ve
ne
zu
ela
_C
lin
ica
l_V
GII
WM
_05_533_B
razil_
Clin
ical_
VG
II
WM
_05_529_B
razil_
Clin
ical_
VG
II
WM_05_274_Colombia_Clinical_VGII
WM
_05_
275_C
olombia
_Clinica
l_VG
II
WM
_04_
84_B
razi
l_C
linic
al_
VG
II
WM_09_94_Australia_Veterinary_VGII
WM
_166
7_VG
III
CD
C_
32
34
A4_Uruguay_Environmental_VGII
B8973_H
I_hum
an_V
GIIW
M_08_311_Austra
lia_Vete
rinary
_VGII
WM
_05_419_Brazil_Clinical_VGII
VGII$
VGIII$
VGIV$
VGI$
C. Gattii major molecular types VGI-VGIVWhole Genome SNP Phylogeny
1,282,876 total SNPs 544,881 p.i.CI of 0.729
Translational Genomics Research Institute | www.tgennorth.org
PNW C. gattii – MLST vs WGST
VGIIa
VGIIb
VGIIc
Gillece et al PLoS One 2011
Translational Genomics Research Institute | www.tgennorth.org
Cryptococcus gattii in PNW
Gillece et al PLoS One 2011
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Translational Genomics Research Institute | www.tgennorth.org
0.01
WM
05.462 BR ST15
WM 05.461 BR ST14
IAL-3234 BR ST137
WM
05.525 BR ST41
IAL-3225 BR ST264
HL_B
11 GR
ST35
HL_
A5
BR
ST12
4W
M 0
5.45
6 B
R S
T17
WM
05.
452
BR
ST
16
WM
05.
457
BR S
T19
HL_
B12
GR
ST1
8
B89
73 H
I ST5
0
WM 08.309 AU ST48
WM 09.83 AU ST48
WM
09.152 AU ST48
B9764 WA ST21
WM
178 AU ST21
HL_A8 BR
ST185
WM
05.533 BR ST11
IAL-3243 B
R S
T283
WM
05.536 BR ST9
WM
1851 VE S
T45
HL_A
2 BR
ST28
WM
05.527 BR
ST
28
WM
04.84 BR
ST
34H
L_B2 B
R S
T248
WM
08.311 AU
ST5
WM
3032 AU
ST
33
WM
11.65 AU
ST
33
WM
05.419 BR
ST
39
WM
05.
547
BR
ST
22
WM
05.
546
BR
ST
23
WM
05.
545
BR
ST
24
HL_
A4
UY
ST
3
WM
05.
274
CO
ST
29
WM
05.
528
BR
ST
40
WM
05.
530
BR
ST
13
WM
09.
94 A
U S
T38
WM
04.
78 C
O S
T31
WM
05.
529
BR
ST2
7
WM 04.78 CO ST31
WM 05.339 CO ST43
WM 06.12 VE ST37
WM 1850 VE ST25
WM 05.342 CO ST25
WM 05.275 CO ST25
HL_A6 AW ST25
ICB-107 BR ST252
B7390 ID ST49
WM 06.10 AR ST20
B8577 BC ST20
B9757 BC ST20
B9759 BC ST20
HL_A1 BC ST20
HL_A11 BC ST20
HL_A3 BC ST20
HL_B5 BC ST20
R265 BC ST20
WM 03.697 BC ST20
WM 05.554 BR ST20
B7436 CA ST20
CA-1014 CA ST20
CBS-7750 CA ST20
HL_B6 DK (BC Travel) ST20
WM 05.432 JP (BR Travel) ST20
B6864 OR ST20
B7422 OR ST20
B7467 OR ST20
B8793 OR ST20
B8849 OR ST20
B9457 OR ST20
B9458 OR ST20
B7395 WA ST20
B8555 WA ST20
NIH-444 WA ST20
WM 03.27 AU ST7
WM 04.71 AU ST7
B9758 BC ST7
R272 BC ST7
WM 05.465 BR ST7
B9588 FL ST7
WM 2552 MY ST7
B7735 OR ST7
B8554 OR ST7
WM 06.634 TH ST7
WM 06.636 TH ST7
B7394 WA ST7
B8828 WA ST7
B9157 WA ST7
B9552 WA ST7
B9563 WA ST7
WM 04.75 TH ST30
B6863 OR ST6
B7432 OR ST6
B7434 OR ST6
B7466 OR ST6
B7491 OR ST6
B7493 OR ST6
B7641 OR ST6
B7737 OR ST6
B7765 OR ST6
B8210 OR ST6
B8214 OR ST6
B8510 OR ST6
B8788 OR ST6
B8798 OR ST6
B8825 OR ST6
B8833 OR ST6
B8843 OR ST6
B9816 OR ST6
B9933 OR ST6
GT-11-7650 OR ST6
HL_B3 OR ST6
HL_B4 OR ST6
B8838 WA ST6
B8571 WA ST6
BA
C
= South America= North America
= Australia= Europe= Asia/Oceana
VGIIa
VGIIc
Phylogenetic Network of C. gattii VGII
Engelthaler et al mBio 2014
VGIIb
Translational Genomics Research Institute | www.tgennorth.org
Hagen et al Plos One 2013
Souto et al. Plos NTD 2016
Billmyre et al mBio 2014
Translational Genomics Research Institute | www.tgennorth.org
7.0
Sample_HL_B5
Cg-B7436
Cg-B8793
Cg-B7422
Cg-B6864
R265_velvet_new
Sample_HL_A11
Cg-NIH-444
Cg-B8577
Cg-B8555
Sample_HL_A3
Sample_HL_A1
Cg-B8849
Cg-CBS-7750
Sample_HL_B6
Cg-B7467
Cg-B7395
21.1008
25.1273
23.388
67.62
18.5283
22.8537
27.0509
23.1263
22.6873
22.3022
18.7634
17.5867
23.9504
9.1512
20.1359
39.0664
1971 (1967-1972)
1983(1978-1988)
Time to Most Recent Common Ancestor
VGIIa BEAST Strict Clock Analysis
Translational Genomics Research Institute | www.tgennorth.org
Root to Tip Distance Method
y = 0.7532x - 12.593R² = 0.5599
0
5
10
15
20
25
30
35
40
45
50
0 10 20 30 40 50 60 70
Ro
ot
to T
ip D
ista
nce
fro
m N
IH44
4 n
od
e
Time after 1950
tMRCA for PNW IIa
Series1
Linear (Series1)
5/15/2017
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Translational Genomics Research Institute | www.tgennorth.org
Modern IIa Samples Only
y = 0.6274x - 1242R² = 0.2626
0
5
10
15
20
25
30
1960 1970 1980 1990 2000 2010 2020
Dis
tan
ce f
rom
Ou
tbre
ak N
od
e
Year
SNPs
Linear (SNPs)
The modern outbreak node is estimated at 1980 (x intercept).
Translational Genomics Research Institute | www.tgennorth.org
9000.0
B6_Denmark_BC_visit_human_VGIIa_2007
B8838_WA_human_VGIIc_2010
B9552_WA_porpoise_VGIIb_2011
WM_09_144_Denmark_BC_visit_human_VGIIa_2006
B7735_OR_Clin_VGIIb_2009
WM_06_12_Ven_Clin_1996
WM_05_456_Brazil_Env_1994
A11_BC_human_VGIIa_2001
WM_05_525_Brazil_Clin_1997
B8554_OR_dog_VGIIb_2008
B7422_OR_cat_VGIIa_2009
B9457_OR_human_VGIIa_2011
WM_05_462_Brazil_Clin_1997
B12_Greece_Clin_1998
B9757_BC_environment_VGIIa_2002
IAL3243_Brazil_Clin_2000
B8214_OR_human_VGIIc_2009
B8798_OR_human_VGIIc_2005
WM_04_75_Thailand_human_VGIIb_1993
WM_05_546_Brazil_Clin_2001
WM_09_83_Aus_Clin_1985
B9816_OR_cat_2012
WM_06_13_USA_environment_VGIIa_1990
B8825_OR_human_VGIIc_2010
WM_05_554_Brazil_human_VGIIa_2002
B11766
B8833_OR_cat_VGIIc_2010
A1_BC_veterinary_VGIIa_2002
B6863_OR_human_VGIIc_2005
WM_05_547_Brazil_Clin_2001
B11442
WM_06_636_Thailand_human_VGIIb_1995
B11566B11569
B9759_BC_cat_VGIIa_2003
B11460
WM_05_419_Brazil_Clin_1988
WM_05_77_Greece_Clin_1998
WM_05_528_Brazil_Clin_2001
B7395_WA_dog_VGIIa_2008
B9758_BC_environment_VGIIb_2002
B7466_OR_cat_VGIIc_2008
B11352
B9563_WA_porpoise_VGIIb_2011
B8849_OR_environment_VGIIa_2010
NIH_444_WA_human_VGIIa_1972
B7641_OR_cat_VGIIc_2008
B11468
B8555_WA_human_VGIIa_2006
WM_05_461_Brazil_Clin_1997
B2_Brazil_Vet_2000
B11562
WM_178_Aus_Clin_1991
B8510_OR_human_VGIIc_2009
B9458_OR_human_VGIIa_2011
WM_05_530_Brazil_Clin_1999
B7737_OR_human_VGIIc_2009
WM_05_545_Brazil_Clin_2001
WM_11_65_Aus_2011
WM_05_465_Brazil_human_VGIIb_1997
WM_05_533_Brazil_Clin_1997
B5_BC_human_VGIIa_2002
B8788_OR_human_VGIIc_2010
B8828_WA_porpoise_VGIIb_2010
B7467_OR_porpoise_VGIIa_2009
B7491_OR_human_VGIIc_2009
B11_Greece_Clin_1996
WM_05_527_Brazil_Clin_1997
WM_05_275_Colombia_Clin_2001
R265_BC_human_VGIIa_2001
B11591
B7735_OR_human_VGIIb_2009
B3_OR_human_VGIIc_2007
WM_09_152_Aus_Env_2009
IAL3234_Brazil_Clin_1998
B4_OR_human_VGIIc_2008
B8210_OR_human_VGIIc_2008
WM_09_94_Aus_2001
B7434_OR_human_VGIIc_2008
A4_Uruguay_Env_1989
WM_06_634_Thailand_human_VGIIb_1994
WM_06_10_Argentina_human_VGIIa_2000
B8577_BC_environment_VGIIa_2009
WM_05_536_Brazil_Clin_1997
WM_03_27_Australia_Env_VGIIb_1992
B6864_OR_human_VGIIa_2004
B8_BC_human_VGIIa_2002
B8973_HI_Clin_2010
B7394_WA_cat_VGIIb_2008
B11428
WM_04_84_Brazil_Clin_VGII_1986
B7436_CA_alpaca_VGIIa_2009
WM_05_452_Brazil_Clin_1995
B8571_WA_human_VGIIc_2009
B8843_OR_human_VGIIc_2010
B11567
B11560
B7390_ID_human_VGIIc_2008
B8825_1_OR_human_VGIIc_2010
B9933_OR_human_VGIIc_2012
WM_04_78_Colombia_Clin_VGII_1998
B9588_FL_human_VGIIb_2012
B7493_OR_sheep_VGIIc_2009
WM_2552_Malaysia_human_VGIIb_1997
IAL3225_Brazil_Clin_1994WM_05_529_Brazil_Clin_1997
WM_05_274_Colombia_Clin_2002
B11441
B11473
B9764_WA_cat_2012
B9157_WA_horse_VGIIb_2011
B7765_OR_dog_VGIIc_2009
WM_06_33_Aruba_1953
WM_05_76_Greece_Clin_1996
B8793_OR_dog_VGIIa_2010
B11592
A3_BC_environment_VGIIa_2002
WM_05_432_Japan_Brazil_human_VGIIa_2000
CBS_7750_CA_environment_VGIIa_1990
B7432_OR_human_VGIIc_2009
WM_06_8_Uru_Env_1996
WM_05_457_Brazil_Clin_1995
Crypto gattii VGII. R265 reference.Rooted with WM11.6586.04% quality breadth, Reference is 17,531,765 bases
VGIIc
VGIIb
VGIIa
2016 PNW Isolates
Translational Genomics Research Institute | www.tgennorth.org
3.0
051 01 52 02 53 0
B11473
B8825_OR_human_VGIIc_2010
B11468
B7737_OR_human_VGIIc_2009
B7432_OR_human_VGIIc_2009
B3_OR_human_VGIIc_2007
B8843_OR_human_VGIIc_2010
B6863_OR_human_VGIIc_2005
B8571_WA_human_VGIIc_2009
B7434_OR_human_VGIIc_2008
B9933_OR_human_VGIIc_2012
B7390_ID_human_VGIIc_2008
B11442
B9816_OR_cat_2012
B8833_OR_cat_VGIIc_2010
B8210_OR_human_VGIIc_2008
B7493_OR_sheep_VGIIc_2009
B7641_OR_cat_VGIIc_2008
B11592
B8510_OR_human_VGIIc_2009
B8838_WA_human_VGIIc_2010
B7491_OR_human_VGIIc_2009
B8798_OR_human_VGIIc_2005
B7765_OR_dog_VGIIc_2009
B8788_OR_human_VGIIc_2010
B11352
B4_OR_human_VGIIc_2008
B7466_OR_cat_VGIIc_2008
B8214_OR_human_VGIIc_2009
VGIIc BEAST AnalysisBased on 10,000 trees,1,000 were burn-inMCC tree =Maximum clade credibilitymid-point rootedTMRCA: 28.7285 years ago95% HPD Interval:[18.7836, 40.9205]
Translational Genomics Research Institute | www.tgennorth.org
Phylogenetics of a Novel Fungus
Apophysomyces
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Translational Genomics Research Institute | www.tgennorth.org
Apophysomyces
Joplin, MissouriMay, 2011
Translational Genomics Research Institute | www.tgennorth.org
Killer Tornado - Joplin, MO May 22, 2011
• EF5 Tornado
• 156 Killed
• 1,100 Hospitalized
• 30-50% of Joplin destroyed
Translational Genomics Research Institute | www.tgennorth.org Translational Genomics Research Institute | www.tgennorth.org
Neblett Fanfair et al. 2012 NEJM
Day 10
PhotosCourtesyGinaWeddle,RN,MSN,CPNP-AC,TheChildren’sMercyHospital
Day 24 Day 102
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Translational Genomics Research Institute | www.tgennorth.org
Apophysomyces spp.
28k SNPs
CI = 0.62
Joplin
Outbreak
Etienne, et al. 2012 PLoS One
Translational Genomics Research Institute | www.tgennorth.org
Genetic vs Geographic Distance
Etienne, et al. 2012 PLoS One
Translational Genomics Research Institute | www.tgennorth.org
Phylogenetics of a Transplant and Medical Contamination OutbreaksCoccidioides, Exserohilum and Sarocladium
Translational Genomics Research Institute | www.tgennorth.org
Valley Fever Transplant Outbreak
• Cocci is opportunistic in organ recipients• In 2010, three solid organ recipients from a
common donor in LA all developed severe Valley Fever – two died
• No samples from donor existed for testing• Needed empirical evidence to determine if all
three were donor-derived or naturally infected
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Translational Genomics Research Institute | www.tgennorth.org
Engelthaler et al 2011 EID
Transplant Outbreak with Coccidioides immitis
Translational Genomics Research Institute | www.tgennorth.org
Fungal Meningitis Outbreakvia Contaminated Injectables
Translational Genomics Research Institute | www.tgennorth.org
Fungal Meningitis - Sept 2012Exserohilum rostratum
• 13,000 people were exposed to three lots of methylprednisolone acetate (MPA)
• >750 cases of fungal meningitis or localized epidural, paraspinal, and peripheral joint infections
• 64 deaths
• Exserohilum found in patients and vials of MPA
Translational Genomics Research Institute | www.tgennorth.org
Whole Genome SNP Typing(WGST)
• 22 E. rostratum isolates from 19 case patients
• 3 isolates from each of two contaminated lots of MPA
• 7 unrelated control E. rostratum isolates
WGST done in parallel at CDC and TGen on different platforms (GAIIx, MiSeq, HiSeq, PacBio) and with
bioinformatic tools (NASP, kSNP)
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Translational Genomics Research Institute | www.tgennorth.org
Exserohilum meningitis from injectable steroid
Litvintseva, et al 2014. JCM
• No more than 2 SNPs between any two outbreak isolates
• ~136K SNPs to the nearest control strain
Translational Genomics Research Institute | www.tgennorth.org
Sarocladium kilienseBlood Stream Infections
Translational Genomics Research Institute | www.tgennorth.org
Sarocladium BSI Outbreak• In January 2014, the Chilean Ministry of Health
reported a cluster of 64 (56 peds) cases of Sarocladium kiliense bloodstream infections
– 8 different hospitals in Santiago, Chile
• All patients had received post-chemotherapy anti-nausea drug Ondansetron
• Subsequently S. killiense was cultured from vials of Ondansetron
• Concurrently, the Columbian Instituto Nacional de Salud identified 16 cases of S. kiliense, originally thought to be Fusarium
Translational Genomics Research Institute | www.tgennorth.org
Sarocladium kiliense
3000.0
B10652, Clinical, Chile
B10971, Clinical, Colombia
B10651, Clinical, Chile
B10661, Vial, Chile
B10648, Clinical, Chile
B10734, Clinical, Colombia
B10650, Clinical, Chile
B10977, Clinical, Colombia
B10979, Vial, Colombia
B10766, Clinical, USA
B5505, Clinical, USA
B10980, Vial, Colombia
B10657, Clinical, Chile
B10764, Clinical, USA
B10748, Vial, Colombia
B10646, Clinical, Chile
CBS155.61, B######, Soil, India
B10731, Clinical, Colombia
B10653, Clinical, Chile
B10765, Clinical, USA
B10973, Clinical, Colombia
B5504, Clinical, USA
B10976, Clinical, Colombia
B10660, Vial, Chile
B10732, Clinical, Colombia
B10978, Vial, Colombia
B10767, Clinical, USA
B10762, Clinical, Germany
B10743, Clinical, Colombia
B10974, Clinical, Colombia
B10763, Clinical, USA
B10972, Clinical, Colombia
ATCC64672, B#####, Dog, Costa Rica
CBS157.61, B#####, Soil, India
B10749, Vial, Colombia
Reference
0
0
1
1693
1
0
0
0
0
2
398
0
17066
3
0
0
0
0
0
11996
13372
0
3461
13273
7171
0
0
3490
4928
1
15195
7550
0
0
01
0
0
2
1
2
4
0
0
199
3
0
2543
0
0
200
1
0
0
2
2
0
12942
0
0
581
1
0
1
440
1
12503
7838
0
0
Etienne, et al. EID 2016
• No more than 4 SNPs between any two outbreak isolates (n=25)
• Except one control (800 SNPs away), ~13K SNPs to the nearest control strain
ATCC64672, Dog, Costa Rica
5/15/2017
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Translational Genomics Research Institute | www.tgennorth.org
Must Haves for This Type of Research
• Global Context for Local Analysis• Multiple Tools for Phylogenetic Understanding• Extensive Resource Access
– Global collaborators– Comprehensive sample repositories– Cutting edge genomic and bioinformatic tools– Highly experienced research team with genomic,
biological, epidemiological, ecological, clinical, and informatics expertise
– Excellent funding sources
Translational Genomics Research Institute | www.tgennorth.org
Translational Genomics Research Inst, USA
Nathan D Hicks
Chandler C Roe
John D Gillece
James M Schupp
Elizabeth M Driebe
Bridget Barker
Marcus Teixeira
Northern Arizona University, USA
Paul S. Keim
Jason Sahl
Centers For Disease Control, USA
Shawn R. Lockhart
Anastasia Litvintseva
Tom Chiller
Julie Harris
Mary Brandt
University of California Davis, USA
George R Thompson III
Arizona Department of Health Services
Victor Waddell
Kenneth Komatsu
Washington State Health Dept
Nicola Marsden-Haug
Westmead Hospital, University of Sydney, AUS
Carolina Firacative
Felix Gilgado
Tania C Sorrell
Wieland Meyer
Australian National University, AUS
Åsa Pérez-Bercoff
Gavin Huttlley
Institut Agronomique néo-Calédonien, NC
Fabian Carriconde
FIOCRUZ, Brazil
Luciana Trilles
Marcia dos Santos Lazera
Instituto Adolfo Lutz, São Paulo-SP, Brazil
Marcia S.C. Melhem
Instituto Nacional de Salud, Bogotá, Colombia
Elizabeth Castañeda
Mahidol University, Bangkok, Thailand
Popchai Ngamskulrungroj
Imperial College, UK
Matthew C. Fisher
University of Birmingham, UK
Kerstin Voelz
Robin C. May
COLLABORATORS
Translational Genomics Research Institute | www.tgennorth.org
Thank You!
“Valley Fever”R. Dillon, 2008