Skurnik_Viikki_08112011

Mikael Skurnik Yersinia

2002- Full professor of Bacteriology (University of Helsinki, Finland) 1998-2002 Academy Research Fellow (Academy of Finland) 1997-98 Director, Turku Centre for Biotechnology (University of Turku, Finland) 1993-97 Academy Research Fellow (Academy of Finland) 1987-93 Head of DNA laboratory (Dept Med Microbiol, Univ of Turku, Finland) 1988 Docent in Molecular Biology (University of Turku, Finland) 1985-87 PostDoc (Hans Wolf-Watz, Ume University, Ume, Sweden) 1985 PhD in Biochemistry (University of Oulu, Finland) 1977 MSc in Biochemistry (University of Oulu, Finland) Main topics: Biosynthesis, genetics and biological role of LPS of genus Yersinia Virulence factors Bacteriophages

Professor of Bacteriology, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland Head of Laboratory, Department of Bacteriology, Helsinki University Central Hospital Laboratory, Helsinki, Finland

08/11/2011 2

Black Death versus discomfort in stomach the pathogenic

Yersiniae

08/11/2011 3

INTRODUCTION

Yersiniae belong to the family Enterobacteriaceae 17 species

Three pathogenic species for humans and animals

Y. pseudotuberculosis and Y. enterocolitica -enteropathogens

Y. pestis causes bubonic and pneumonic plague

Genus Yersinia

Mikael Skurnik / Haartman Institute / University of Helsinki

Y. enterocolitica

-subsp palearctica

- subsp enterocolitica

Y. pestis

Y. pseudotuberculosis

Y. ruckerii

Y. aldovae

Y. aleksiciae

Y. bercovieri

Y. entomophaga

Y. frederiksenii

Y. intermedia

Y. kristensenii

Y. massiliensis

Y. mollareti

Y. nurmii

Y. pekkanenii

Y. rohdei

Y. similis

17 species Pathogens and environmental strains

1939

1894

1883

1979

1984

2005

1988

2010

1980

1980

1980

2008

1988

2010

2010

1987

2008


The Yersinia

infections

Yersiniae make a good

model because:

(i) Yersiniae possess tens of

recognised virulence factors

and

(ii) there are good animal

models for the disease.

08/11/2011 6

Taxonomy and History

Y. pseudotuberculosis was first described by Malassez and Vignal in 1883 after isolating it from tubercle-like abscesses from infected animals

Numerous names: bacille de la tuberculose zooglique

Bacillus pseudotuberculosis

Bacterium pseudotuberculosis rodentium

Pasteurella pseudotuberculosis

Y. pseudotuberculosis in 1974

08/11/2011 7


Y. enterocolitica was described in 1939 by

Schleifstein and Coleman

Bacterium enterocoliticum

Pasteurella pseudotuberculosis-like

Pasteurella pseudotuberculosis type B

Pasteurella X

Pasteurella Y

Germe X

Y. enterocolitica in 1964

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Bacteriological Properties

Like other Enterobacteriaceae

Y. enterocolitica and Y. pseudotuberculosis are gram-

negative, aero-anaerobic rods

Properties that distinguish them

Motile only at temperatures

08/11/2011 9


Y. enterocolitica turned out to be

heterogeneous:

in addition to Y. enterocolitica sensu stricto

contained several related "Y. enterocolitica-like"

species

08/11/2011 10


Y. aldovae

Y. aleksiciae

Y. bercovieri

Y. entomophaga

Y. frederiksenii

Y. intermedia

Y. kristensenii

Y. mollaretii

Y. nurmii

Y. pekkanenii

Y. rohdei

Y. similis

Non-pathogenic species

08/11/2011 11


Y. ruckeri

An important fish pathogen responsible for

the red mouth disease

Its classification in the genus Yersinia is

controversial

08/11/2011 12

Infections

Y. pseudotuberculosis infects a wider range of

animals than Y. enterocolitica

Its importance in human infections is much lower

than that of Y. enterocolitica worldwide

Both are transmitted by the oral route

Cause intestinal symptoms

Abdominal pain (Y. pseudotuberculosis)

Diarrhea (Y. enterocolitica)

Fever

08/11/2011 13

Evolutionary Remarks

Y. enterocolitica is the most distantly

related pathogenic species of Yersinia

Y. pestis and Y. pseudotuberculosis

should be included into a single species

Not accepted for practical reasons

08/11/2011 14

Relatedness at DNA level

Y. pestis

Y. pseudotuberculosis >90 %

Y. enterocolitica ~50 %

Other Enterobacteria

08/11/2011 15


Y. pstb ancestor Y. enterocolitica ~50 % identical

Y. pestis

Y. pstb serotypes

42187 Myrs

0.4 to 1.9 Myrs

Yersinia ancestor

08/11/2011 16

prehistoric plague in Middle-Asian plateau ?

gradually spread to other parts of the world

required dense population and low hygiene levels

Bible tells in Samuels book of plague among Philisteans at 1320 BC

3 pandemics

1st: 541-700

2nd: 1347-1700

3rd: 1855-1920

History of bubonic plague

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History of bubonic plague

The Black Death

Killed more people than any other disease on earth

Ca. 200 million during known history

08/11/2011 18

Started late in the 19th century in Far East

3rd pandemic of plague

1894 came to Kanton and Hong-Kong

the plague bacillus isolated in Hong-Kong

Alexandre Yersin

a bacteriologist from Institut Pasteur who was commissioned

to Hong-Kong to study the outbreak

Small epidemics until 1950

war in Vietnam

Improved hygienic conditions

08/11/2011 19

Zoonosis mainly in rodents

Lifecycle of plague

Man does not have importance to the long range survival of plague bacillus

Fleas function as spreading vectors between rodents

blood meal of fleas carry the bacteria

infection restricted to their alimentary tract

08/11/2011 20

A 0.03 - 0.5 l blood meal from the rat

~300 bacteria or more

bacteria grow and block the proventriculus

flea cannot swallow new blood

Lifecycle of plague In the flea

Hungry flea tries to eat repeatedly

blood in aesophagus contaminated with bacteria

regurgitated back into wound

10000 - 25000 bacteria

08/11/2011 21

PMN phagocytose and kill most bacteria

Bacteria survive and grow in monocytes

become resistant to phagocytosis

Lifecycle of plague In the mammal

From the initial infection site bacteria move to local lymph nodes proliferates explosively

a bubo forms = swollen lymph node

bacteria gain entry to bloodstream

08/11/2011 22

To spread efficiently

sepsis is needed

high enough concentration of bacteria

flea gets infected while eating


spread to liver and spleen strong growth in blood, liver and

spleen

spread to other organs, e.g., lungs

the circle closes

08/11/2011 23

Death is caused by degrading bacteria

Buboes and skin are dark in color endotoxin induced TNF mediated

leakage of capillaries

Black Death

Endotoxic shock final cause of death


08/11/2011 Helsinki ABS - December 17, 2007 24

Genomic maximum parsimony tree and divergence dates based on 1,364 non-repetitive, non-homoplastic SNPs from 3,349 coding sequences in 16 Y. pestis genomes . Morelli et al. Nat Gen. 2010

Evolution of Y. pestis

08/11/2011 25

Fully parsimonious minimal spanning tree of 933 SNPs for 282 isolates of Y. pestis colored by location. Morelli et al. Nat Gen. 2010

country-specific lineages

08/11/2011 26


Y. pstb ancestor Y. enterocolitica ~50 % identical

Y. pestis

Y. pstb serotypes

42187 Myrs

0.4 to 1.9 Myrs

Yersinia ancestor

MLST analysis of Y. pstb

Laukkanen-Ninios et al. Environmental Microbiology 2011.

417 Y. pstb strains included

Y. pstb is a complex of 4 populations

Y. pseudotuberculosis s.s.

Y. pestis

Y. similis

Korean group

08/11/2011 27

08/11/2011 28

MLST

Continents Asia Europe -collection bias?

08/11/2011 29

MLST

Serotypes Flaws in serotyping ? Horizontal gene transfer HGT

08/11/2011 30

MLST

Serotypes O:6 Flaws in serotyping ? Horizontal gene transfer HGT

08/11/2011 31

MLST


08/11/2011 32

MLST


08/11/2011 33

MLST


08/11/2011 34

MLST


08/11/2011 35

MLST


08/11/2011 36

MLST


O:2a

08/11/2011 37

MLST


O:2b

08/11/2011 38

MLST


O:2c

08/11/2011 39

MLST

Serotypes Flaws in serotyping ? Horizontal gene transfer HGT

08/11/2011 40

MLST

Serotypes

O:1b O:1a

Y. pestis

Y. enterocolitica

08/11/2011 41

08/11/2011 42

Reservoir

A wide variety of ecological niches may

shelter Y. enterocolitica including

the environment (soil, water)

food (milk, retailed meat products, vegetables,

eggs, cheese, etc.)

08/11/2011 43

Reservoir

a wide range of animals

domestic (cat, dog)

stock farming (chinchilla, mink, pigs, rabbit, cow,

goose, horse, sheep, buffalo) or zoo (monkey)

wild (raccoon, fox, snail, frog, beaver, deer, ocelot,

crab, flies, fleas), birds (robin), shelfish (oyster)

many species of small rodents

08/11/2011 44

Transmission by Food

Infected vegetables

The ability of Yersinia to multiply at 4 C is an important factor to take into consideration

Storage of food in refrigerators reason for the "explosion" of yersiniosis cases in the 50's A low number of pathogenic Y. enterocolitica in food may not

cause any symptom if consumed immediately

The same product kept in the refrigerator will be heavily loaded with Yersinia after a few days and may then cause a disease

Infective inoculum required to cause intestinal symptoms ca. 109 bact/ml

08/11/2011 45

Heterogeneity of Y. enterocolitica

Pathogenic and non-pathogenic (environmental) strains

European and American pathogenic strains

pathogenic serotypes

pathogenic biotypes

Y. enterocolitica like species

virulence genes

08/11/2011 46

Y. enterocolitica Biotypes

Y. enterocolitica strains classify into 5

biotypes

Reaction 1A 1B 2 3 4 5

Esculin (< 24h) + - - - - -

Pyrazinamidase + - - - - -

Tween esterase + + - - - -

Indole + + (+) - - -

Xylose + + + + - v

Trehalose + + + + + -

NO3 + + + + + -

08/11/2011 47

Y. enterocolitica Serotypes

>75 somatic antigens (O-antigens) in Y.

enterocolitica and the related species

A large number of flagellar antigens

Different Yersinia species and biotypes may

share common O-antigens

08/11/2011 48

Y. enterocolitica Serotypes

The O:3, O:9 or O:8 O-antigens are regularly found in pathogenic strains

They are not strictly pathogen-specific, though

also in non-pathogenic species or biotypes O:8 in Y. bercovieri or in biotype 1A

O:9 in Y. frederiksenii

O:1,2,3 in biotype 1A

O:3 in Y. mollaretii

LPS types

08/11/2011 49

08/11/2011 50

Y. enterocolitica Types

Biotype 1A strains are non-pathogenic

Ubiquitous

Often found in food and in the environment

Are occasionally encountered in the

digestive tract of animals and humans

Many O-antigens

O:5, O:6 and O:7,8 are the most common

2006 in Finland 462 human isolates: O:3 77 O:9 5 1A 299 Y.e.-like strains 79

Y. frederiksenii, Y. bercovieri, Y. mollaretii Anja Siitonen KTL

MLST

08/11/2011 51

0.1

FE80202 O:8

FE80216 O:8

FE81891 O:8

FE81870 O:8

FE80257 O:6

FE81171 O:6

FE80088 O:5

FE80140 O:6

FE80947 O:5

FE80079 O:5

FE80044

FE82539

FE81507 rough

FE80178 rough

FE81536

FE80766

FE81435

FE81225

FE81455 O:6

FE81835

FE81006 O:10

FE83264 O:10

FE80470 O:6

FE82326 O:6

FE81892

FE82588

FE81836 rough

FE81228 rough

FE81875

FE80447 O:8

FE82009

FE80648

FE81173

FE80150

FE81890 rough

FE81079

FE81278

FE80938

NCTC 11176 4/O:3

FE80016 4/O:3

FE82162 4/O:3

FE83306 4/O:3

FE80665 4/O:3

FE81568 3/O:3

FE80256 2/O:9

FE83011 2/O:9

FE83088 2/O:9

NCTC 11174 2/O:9

8081 1B/O:8

FE80647 O:10

FE81527 O:10

FE81346 O:10

FE81454 O:10

FE81593 O:10

ATCC 33638 Y. kristensenii

ATCC 35236 Y. aldovae

ATCC 33641 Y. frederiksenii

ATCC 43380 Y. rohdei

ATCC 43970 Y. bercovieri

ATCC 43969 Y. mollaretii

ATCC 29909 Y. intermedia

ATCC 29473 Y. ruckeri

Y. enterocolitica

ssp. palearctica

BT 1A genetic group I

Y. enterocolitica ssp.

palearctica BTs 2-4

BT 1A genetic group II

Y. enterocolitica

ssp. enterocolitica

75

77

100

98

100

81

91

100

100

100

100

100

100

0.1

FE80202 O:8

FE80216 O:8

FE81891 O:8

FE81870 O:8

FE80257 O:6

FE81171 O:6

FE80088 O:5

FE80140 O:6

FE80947 O:5

FE80079 O:5

FE80044

FE82539

FE81507 rough

FE80178 rough

FE81536

FE80766

FE81435

FE81225

FE81455 O:6

FE81835

FE81006 O:10

FE83264 O:10

FE80470 O:6

FE82326 O:6

FE81892

FE82588

FE81836 rough

FE81228 rough

FE81875

FE80447 O:8

FE82009

FE80648

FE81173

FE80150

FE81890 rough

FE81079

FE81278

FE80938

NCTC 11176 4/O:3

FE80016 4/O:3

FE82162 4/O:3

FE83306 4/O:3

FE80665 4/O:3

FE81568 3/O:3

FE80256 2/O:9

FE83011 2/O:9

FE83088 2/O:9

NCTC 11174 2/O:9

8081 1B/O:8

FE80647 O:10

FE81527 O:10

FE81346 O:10

FE81454 O:10

FE81593 O:10









0.1

FE80202 O:8

FE80216 O:8

FE81891 O:8

FE81870 O:8

FE80257 O:6

FE81171 O:6

FE80088 O:5

FE80140 O:6

FE80947 O:5

FE80079 O:5

FE80044

FE82539

FE81507 rough

FE80178 rough

FE81536

FE80766

FE81435

FE81225

FE81455 O:6

FE81835

FE81006 O:10

FE83264 O:10

FE80470 O:6

FE82326 O:6

FE81892

FE82588

FE81836 rough

FE81228 rough

FE81875

FE80447 O:8

FE82009

FE80648

FE81173

FE80150

FE81890 rough

FE81079

FE81278

FE80938

NCTC 11176 4/O:3

FE80016 4/O:3

FE82162 4/O:3

FE83306 4/O:3

FE80665 4/O:3

FE81568 3/O:3

FE80256 2/O:9

FE83011 2/O:9

FE83088 2/O:9

NCTC 11174 2/O:9

8081 1B/O:8

FE80647 O:10

FE81527 O:10

0.1

FE80202 O:8

FE80216 O:8

FE81891 O:8

FE81870 O:8

FE80257 O:6

FE81171 O:6

FE80088 O:5

FE80140 O:6

FE80947 O:5

FE80079 O:5

FE80044

FE82539

FE81507 rough

FE80178 rough

FE81536

FE80766

FE81435

FE81225

FE81455 O:6

FE81835

FE81006 O:10

FE83264 O:10

FE80470 O:6

FE82326 O:6

FE81892

FE82588

FE81836 rough

FE81228 rough

FE81875

FE80447 O:8

FE82009

FE80648

FE81173

FE80150

FE81890 rough

FE81079

FE81278

FE80938

NCTC 11176 4/O:3

FE80016 4/O:3

FE82162 4/O:3

FE83306 4/O:3

FE80665 4/O:3

FE81568 3/O:3

FE80256 2/O:9

FE83011 2/O:9

FE83088 2/O:9

NCTC 11174 2/O:9

8081 1B/O:8

FE80647 O:10

FE81527 O:10

FE81346 O:10

FE81454 O:10

FE81593 O:10









Y. enterocolitica

ssp. palearctica

BT 1A genetic group I

Y. enterocolitica ssp.

palearctica BTs 2-4

BT 1A genetic group II

Y. enterocolitica

ssp. enterocolitica

75

77

100

98

100

81

91

100

100

100

100

100

100

Sihvonen et al, submitted. MLSA-tree constructed of concatenated sequences of seven house-keeping genes(4580 bp) of 62 yersinia strains Four major phylogenetic clusters of YE strains

Genus Yersinia


Y. enterocolitica

-subsp palearctica

- subsp enterocolitica

Y. pestis


Y. ruckerii

Y. aldovae

Y. aleksiciae

Y. bercovieri

Y. entomophaga

Y. frederiksenii

Y. intermedia

Y. kristensenii

Y. massiliensis

Y. mollareti

Y. nurmii

Y. pekkanenii

Y. rohdei

Y. similis

17 species Pathogens and environmental strains

1939

1894

1883

1979

1984

2005

1988

2010

1980

1980

1980

2008

1988

2010

2010

1987

2008

08/11/2011 53

Relatedness at DNA level

Y. pestis

Y. pseudotuberculosis >90 %

Y. enterocolitica ~50 %

Other Enterobacteria

08/11/2011 54

Variation between strains

Serotypes Biotypes

Y. pestis no 3

Y. pseudotuberculosis 21 no (2)

Y. enterocolitica ~70 many

LPS O-antigen

08/11/2011 55

Differences between species

Virulence LD50

Y. pestis High

08/11/2011 56

70 kb virulence plasmid

Virulence factors of Y. pestis

Type III secretion system delivers >10 Yops - cytotoxins and immuno-suppressing factors

Fraction 1 capsule Inhibition of phagocytosis

Fibrillar adhesin pH 6 antigen

Pigmentation and iron uptake

Flea and mammals

Plasminogen activator Pla

Invasion in tissues


Genome

4.4 million bp

(Sanger)

Y. pestis genetics

70 kb

plasmid

9.5 kb

plasmid

Silenced genes

Insertion sequences

100 kb

plasmid

08/11/2011 58

Genome, 4.4 million bp

LPS, 21 O-serotypes

Invasin


70 kb plasmid

Type III Secr.

YadA

Insertion sequences

08/11/2011 59

Genome

4.4 million bp

LPS, 21 O-serotypes

Invasin

Y. pstb Y. pestis

70 kb plasmid

Type III Secr.

YadA

9.5 kb plasmid

Pla

Insertion sequences

100 kb plasmid Fraction 1 Capsule

Murine Toxin

Silenced genes

08/11/2011 60

How?

Horizontal transfer of new plasmids

100 kb plasmid

9.5 kb plasmid

silencing of genes (ca. 300 pseudogenes)

O-antigen gene cluster

inv IS-element

YadA-expressing Y.

pestis is less virulent

Rosqvist, Skurnik & Wolf-

Watz. Nature, 1988

Y. pestis AGGTCCAG.A AAAAAAAGAG CTAGATTAGC

Y. Pstb AGGTCCAGAA AAAAAAAGAG CTAGATTAGC

yadA

08/11/2011 61

Evolution of the research

Bacteriophage receptor in Yersinia enterocolitica serotype O:3 the LPS outer core

Cloning and sequencing of the gene cluster

How did I get involved?

Sewage of the City of Turku bacteriophage fR1-37

Mol. Microbiol. 17: 575-594, 1995

08/11/2011 62

LPS gene clusters in Yersinia

adk hemH gsk

Y. enterocolitica O:3 outer core gene cluster

adk hemH

Ye O:8

gsk

Y. pseudotuberculosis O-antigen gene cluster

Y. enterocolitica O:8 O-antigen gene cluster

hemH gsk

adk

What about Y. pestis?

~20 kb

~20 kb

~13 kb 13.3.1996

28.3.1996

30.3.1996

~20 kb, 30.3.1996 !!!!

Long Range PCR

08/11/2011 63

Goals

Analysis of this locus in Y. pestis

comparison of Y. pestis locus to the loci of 21 serotypes of Y. pseudotuberculosis

08/11/2011 64

The gene clusters

Y. pseudotuberculosis O:1b

Y. pestis

100 100 100 100 99.3 99.1 90.4 98.3 100 100 99.7 99.8 100 99.8 99.6 99.8 98.7

Repeats

Repeats

08/11/2011 65

Y. pstb O:1b O-antigen structure and biosynthesis

Paratose

Mannose Mannose L-Fucose GlcNAc-

1,3

1,2 1,4 1,3 1,3 1,2

n

manA

glmS

glmU

wecA

08/11/2011 66

Y. pestis O-antigen cluster defects

Paratose

Mannose Mannose L-Fucose GlcNAc-

1,3

1,2 1,4 1,3 1,3 1,2

n

08/11/2011 67

The mutations CDP-Paratose biosynthesis

...DdhB G A T V K G Y S L T A P T V P S L F E

GGGGCAACGGTAAAAGGTTACTCTCTG..ACCGCCCCCACTGTGCCTAGCCTATTTGAG 2660 O:1b

|||||||||||||||||||||||| || || ||||||| ||||||||||||||||||

GGGGCAACGGTAAAAGGTTACTCTTTG.CCCCCCCCCCACGGTGCCTAGCCTATTTGAG EV76

||||||||||||||||||||||||||| |||||||||||||||||||||||||||||||

GGGGCAACGGTAAAAGGTTACTCTTTGCCCCCCCCCCCACGGTGCCTAGCCTATTTGAG CO 92

1-2 bp insertions in ddhB of Y.pestis

08/11/2011 68

The mutations O-antigen polymerase

... Wzy A G K I F F I N V L L F V L L E L L K

GCCGGAAAGATTTTTTTT.ATTAATGTGCTTCTATTTGTATTACTTGAGTTATTAAAAGG 11370 O:1b

|||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||

GCCGGAAAGATTTTTTTTTATTAATGTGCTTCTATTTGTATTACTTGAGTTATTAAAAGG Y. pestis

1 bp insertion in wzy of Y.pestis

08/11/2011 69

The mutations Paratosyltransferase

... WbyI I R W I Q K Y G P I K Y N K T K V S Y Y R I L D N E S M R P

ATTAGGTGGATTCAAAAGTATGGACCAATAAAATATAATAAAACTAAAGTCTCCTATTATAGAATTCTCGATAATGAAAGTATGAGGCCA

|||||||||||||| ||||||||||||||

ATTAGGTGGATTCA..............................................................AAAGTATGAGGCCA

62 bp deletion in wbyI of Y.pestis

Short range homologous recombination

08/11/2011 70

The mutations Fucose

...Gmd H G I K R S P Y A V A K M Y A Y W I T V N

CATGGTATTAAGCGTTCTCC.TTATGCTGTTGCCAAAATGTATGCTTACTGGATTACAGTAA 13900 O:1b

|||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||||

CATGGTATTAAGCGTTCTCCTTTATGCTGTTGCCAAAATGTATGCTTACTGGATTACAGTAA Y. pestis

1 bp insertion in gmd of Y.pestis

... Fcl A A A K V G G I Q A N N N Y P A E F I Y Q

GCTGCGGCAAAAGTGGGGGGGATTCAGGCCAATAATAATTATCCGGCAGAGTTCATCTACCAA 14765 O:1b

|||||||||||||||||||| ||||||||||||||||||||||||||||||||||||||||||

GCTGCGGCAAAAGTGGGGGG.ATTCAGGCCAATAATAATTATCCGGCAGAGTTCATCTACCAA Y. pestis

1 bp deletion in fcl of Y.pestis

08/11/2011 71

O:1b vs. Y.pestis Intergenic repeats

83 bp insertion:

6 TTTAATAA- and 5 TTAAAAG-repeats in Y. pseudotuberculosis O:1b

... WbyH Y S S I *

TATAGTTCAA TTTAATAA TTTAATAA TTTAATAA TTTAATAA TTTAATAA TTTAATAA TTTAATAA

|||||||||| ||||||||

TATAGTTCAA TTTAATAA ......... ....... ........ ........ ........ ........

TTAAAAG TTAAAAG TTAAAAG TTAAAAG TTAAAAG TTAAAAG TTAAAAG TTAATATAC 7200 O:1b

|||||| ||| || |||||||||

....... ....... ....... ....... ....... TTAAAAT CTAACAG TTAATATAC Y. pestis

08/11/2011 72

O:1b vs. Y.pestis Intergenic repeats

... Fcl

H Q N N F R K *

CATCAGAATAACTTCAGAAAATAGTTTC ....... ....... ....... ....... ....... ....... ....... ....... ....... ....... ....... ATTTGCT ATTTGCT ATTTGCT ATTTGGATATGGCG 15524 O:1b

|||||||||||||||||||||||||||| ||||||| ||||||| ||||||| ||||||||||||||

CATCAGAATAACTTCAGAAAATAGTTTC ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGGATATGGCG EV76

|||||||||||||||||||||||||||| ||||||| ||||||| ||||||| ||||||| ||||||| ||||||| ||||||||||||||

CATCAGAATAACTTCAGAAAATAGTTTC ....... ....... ....... ....... ....... ....... ....... ....... ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGGATATGGCG CO 92

21-77 bp insertions = 3-11 extra copies

of ATTTGCT in Y. pestis strains

14 repeats in EV76 6 repeats in CO92

3 repeats in O:1b


Genomic maximum parsimony tree and divergence dates based on 1,364 non-repetitive, non-homoplastic SNPs from 3,349 coding sequences in 16 Y. pestis genomes . Morelli et al. Nat Gen. 2010

Evolution of Y. pestis


Thank You! Anja Siitonen

Mark Achtman et al.

Hiroshi Fukushima

Elisabeth Carniel

Hannu Korkeala

Leila Sihvonen

Susanna Toivonen

Riikka Laukkanen-Ninios

Date post:	07-Jan-2016
Category:	Documents
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