Skurnik Viikki 08112011

Mikael Skurnik
Yersinia
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
2002Full 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
Black Death versus discomfort in

stomach the pathogenic
Yersiniae
08/11/2011
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
08/11/2011
Genus Yersinia
Y. enterocolitica
-subsp palearctica
- subsp enterocolitica
Y. pestis
Y. pseudotuberculosis
Y. ruckerii
1939
1894
1883
1979
17 species
Pathogens and environmental strains
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
Mikael Skurnik / Haartman Institute / University of Helsinki
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.
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:
08/11/2011
bacille de la tuberculose zooglique

Bacillus pseudotuberculosis
Bacterium pseudotuberculosis rodentium
Pasteurella pseudotuberculosis
Y. pseudotuberculosis in 1974
6
Y. enterocolitica was described in 1939 by

Schleifstein and Coleman
08/11/2011
Bacterium enterocoliticum
Pasteurella pseudotuberculosis-like
Pasteurella pseudotuberculosis type B
Pasteurella X
Pasteurella Y
Germe X
Y. enterocolitica in 1964
7
Bacteriological Properties
Like other Enterobacteriaceae
Y. enterocolitica and Y. pseudotuberculosis are gramnegative, aero-anaerobic rods
Properties that distinguish them
08/11/2011
Motile only at temperatures <30 C

They form colonies in 48 h instead of 24 h
Their optimal growth temperature is around 30 C
They are able to multiply at low temperatures (4 C)
Their G+C content (46-49%) is slightly lower than that of
others
Y. enterocolitica turned out to be

heterogeneous:
in addition to Y. enterocolitica sensu stricto

contained several related "Y. enterocolitica-like"
species
08/11/2011
Y. aldovae
Y. aleksiciae
Y. bercovieri
Y. entomophaga
Y. frederiksenii
Y. intermedia
Y. kristensenii
Y. mollaretii
Y. nurmii
Y. pekkanenii
Y. rohdei
Y. similis
08/11/2011
Non-pathogenic species
10
Y. ruckeri
An important fish pathogen responsible for

the red mouth disease
Its classification in the genus Yersinia is
controversial
08/11/2011
11
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
12
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
08/11/2011
Not accepted for practical reasons
13
Relatedness at DNA level

Y. pestis
>90 %
Y. enterocolitica
~50 %
Other Enterobacteria
<20 %
08/11/2011
14
Yersinia ancestor
42187 Myrs
Y. pstb ancestor
0.4 to 1.9 Myrs
Y. enterocolitica
~50 % identical
Y. pstb serotypes
<20000 years (last estimate ~5000 yr)
Y. pestis
08/11/2011
15
History of bubonic plague
3 pandemics
1st: 541-700
2nd: 1347-1700
3rd: 1855-1920
prehistoric plague in
Middle-Asian plateau ?
08/11/2011
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
16
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
17
3rd pandemic of plague
Started late in the 19th century in Far East
1894 came to Kanton and Hong-Kong
Small epidemics until 1950
the plague bacillus isolated in Hong-Kong

Alexandre Yersin
a bacteriologist from Institut Pasteur who was commissioned
to Hong-Kong to study the outbreak
war in Vietnam
Improved hygienic conditions
08/11/2011
18
Lifecycle of plague
Zoonosis mainly in rodents
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
19
Lifecycle of plague
In the flea
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
Hungry flea tries to eat repeatedly
blood in aesophagus
contaminated with bacteria
regurgitated back into wound
10000 - 25000 bacteria
08/11/2011
20
Lifecycle of plague
In the mammal
PMN phagocytose and kill most bacteria
Bacteria survive and grow in monocytes

become resistant to phagocytosis
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
21
Lifecycle of plague
In the mammal
spread to liver and spleen
To spread efficiently
strong growth in blood, liver and

spleen
spread to other organs, e.g., lungs
sepsis is needed
high enough concentration of bacteria
flea gets infected while eating
the circle closes

08/11/2011
22
Lifecycle of plague
In the mammal
Buboes and skin are dark in

color
endotoxin induced TNF mediated

leakage of capillaries
Black Death
Death is caused by
degrading bacteria
Endotoxic shock final

cause of death
08/11/2011
23
Evolution of
Y. pestis
Genomic maximum parsimony

tree and divergence dates based
on 1,364 non-repetitive, nonhomoplastic SNPs from 3,349
coding sequences in 16 Y. pestis
genomes .
Morelli et al. Nat Gen. 2010
08/11/2011
Helsinki ABS - December 17, 2007
24
Fully parsimonious minimal spanning tree of 933 SNPs for 282 isolates of Y. pestis colored by location.
country-specific lineages
08/11/2011
25
Yersinia ancestor
42187 Myrs
Y. pstb ancestor
0.4 to 1.9 Myrs
Y. enterocolitica
~50 % identical
Y. pstb serotypes
horizontal
<20000 years (lastMLST
estimate
~5000 yr)gene transfer
Y. pestis
08/11/2011
26
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
MLST
Continents
Asia
Europe
-collection bias?
08/11/2011
28
MLST
Serotypes
Flaws in serotyping ?
Horizontal gene transfer HGT
08/11/2011
29
MLST
Serotypes O:6
08/11/2011
30
MLST
Serotypes O:7
08/11/2011
31
MLST
Serotypes O:9
08/11/2011
32
MLST
Serotypes O:11
08/11/2011
33
MLST
Serotypes O:15
08/11/2011
34
MLST
Serotypes O:2
08/11/2011
35
MLST
Serotypes O:2
O:2a
08/11/2011
36
MLST
Serotypes O:2
O:2b
08/11/2011
37
MLST
Serotypes O:2
O:2c
08/11/2011
38
MLST
Serotypes
08/11/2011
39
MLST
Serotypes
Y. pestis
O:1b
08/11/2011
O:1a
40
Y. enterocolitica
08/11/2011
41
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
42
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
43
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
44
Heterogeneity of Y. enterocolitica
Pathogenic and non-pathogenic

(environmental) strains
08/11/2011
European and American pathogenic strains

pathogenic serotypes
pathogenic biotypes
Y. enterocolitica like species
virulence genes
45
Y. enterocolitica Biotypes
Y. enterocolitica strains classify into 5

biotypes
Reaction
08/11/2011
1A
1B
Esculin (< 24h)
Pyrazinamidase
Tween esterase
Indole
(+)
Xylose
Trehalose
NO3
46
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
47
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
08/11/2011
48
LPS types
08/11/2011
49
Y. enterocolitica Types
2006
in Finland
human are
isolates:
Biotype
1A462strains
non-pathogenic
O:3 77
Ubiquitous
O:9
5
Often
1A
299 found in food and in the environment
Y.e.
strains 79 encountered in the
Are-like
occasionally
Y. frederiksenii, Y. bercovieri, Y. mollaretii
digestive tract of animals and humans
Anja Siitonen KTL
Many O-antigens
O:5, O:6 and O:7,8 are the most common
08/11/2011
50
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
MLST
FE80079 O:5
FE80044
FE82539
FE81507 rough
FE80178 rough
75
FE81536
FE80766
FE81435
FE81225
FE81455 O:6
Y. enterocolitica
ssp. palearctica
BT 1A genetic group I
FE81835
FE81006 O:10
FE83264 O:10
FE80470 O:6
FE82326 O:6
FE81892
FE82588
FE81836 rough
FE81228 rough
FE81875
Sihvonen et al, submitted.
FE80447 O:8
FE82009
77
FE80648
FE81173
FE80150
MLSA-tree constructed of concatenated

sequences of seven house-keeping
genes(4580 bp) of 62 yersinia strains
FE81890 rough
FE81079
FE81278
FE80938
NCTC 11176 4/O:3
100
FE80016 4/O:3
FE82162 4/O:3
Four major phylogenetic clusters of YE

strains
FE83306 4/O:3
FE80665 4/O:3
FE81568 3/O:3
Y. enterocolitica ssp.
palearctica BTs 2-4
FE80256 2/O:9
98 FE83011 2/O:9
100
FE83088 2/O:9
NCTC 11174 2/O:9
8081 1B/O:8
100
FE80647 O:10
100
100
Y. enterocolitica
ssp. enterocolitica
FE81527 O:10
FE81346 O:10
100
100
FE81454 O:10
FE81593 O:10
BT 1A genetic group II
ATCC 33638 Y. kristensenii
81
ATCC 35236 Y. aldovae

ATCC 33641 Y. frederiksenii
91
ATCC 43380 Y. rohdei

ATCC 43970 Y. bercovieri
100
ATCC 43969 Y. mollaretii

ATCC 29909 Y. intermedia
ATCC 29473 Y. ruckeri
0.1
08/11/2011
51
Genus Yersinia
Y. enterocolitica
-subsp palearctica
- subsp enterocolitica
Y. pestis
Y. ruckerii
1939
1894
1883
1979
17 species
Pathogens and environmental strains
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
1984
2005
1988
2010
1980
1980
1980
2008
1988
2010
2010
1987
2008
Relatedness at DNA level

Y. pestis
>90 %
Y. enterocolitica
~50 %
Other Enterobacteria
<20 %
08/11/2011
53
Variation between strains

Serotypes
Biotypes
Y. pestis
no
21
no (2)
Y. enterocolitica
~70
many
LPS O-antigen
08/11/2011
54
Differences between species
Y. pestis
Y. pseudotub.
Y. enterocolitica
08/11/2011
Virulence
LD50
High
<10
Medium
10 -10
Medium - No
10 -10
55
Virulence factors of Y. pestis

Pigmentation and iron
uptake
70 kb virulence plasmid
Plasminogen activator
Pla
Fraction 1 capsule
pH 6 antigen
08/11/2011
Flea and mammals

Type III secretion system delivers >10
Yops - cytotoxins and immuno-suppressing
factors
Invasion in tissues
Inhibition of phagocytosis
Fibrillar adhesin
56
Y. pestis genetics
70 kb
plasmid
Genome
4.4 million bp
(Sanger)
Silenced genes
Insertion sequences
08/11/2011
9.5 kb
plasmid
100 kb
plasmid
57
Genome, 4.4 million bp

LPS, 21 O-serotypes
Invasin
70 kb
plasmid
Type III Secr.
YadA
Insertion sequences
08/11/2011
58
Y. pstb Y. pestis
70 kb
plasmid
9.5 kb plasmid
Pla
Genome
4.4 million bp
Type III Secr.
LPS, 21 O-serotypes YadA
100 kb plasmid
Invasin
Silenced genes
Insertion sequences
08/11/2011
Fraction 1 Capsule
Murine Toxin
59
How?
Horizontal transfer of new plasmids
100 kb plasmid
9.5 kb plasmid
silencing of genes (ca. 300 pseudogenes)
yadA
Y. pestis AGGTCCAG.A AAAAAAAGAG CTAGATTAGC

Y. Pstb
AGGTCCAGAA AAAAAAAGAG CTAGATTAGC
inv
O-antigen gene cluster
08/11/2011
IS-element
YadA-expressing Y.
pestis is less virulent
Rosqvist, Skurnik & WolfWatz. Nature, 1988
60
Evolution of the research
How did I get involved?

Sewage of the City of Turku
Bacteriophage receptor in Yersinia

enterocolitica serotype O:3
bacteriophage fR1-37
the LPS outer core
Cloning and sequencing of the gene

Mol. Microbiol. 17: 575-594, 1995
cluster
08/11/2011
61
LPS gene clusters in Yersinia

Long Range PCR
~13 kb
Y. enterocolitica O:3 outer core gene cluster
adk hemH
13.3.1996
gsk
~20 kb
Y. enterocolitica O:8 O-antigen gene cluster
adk
28.3.1996
gsk
hemH
~20 kb
Y. pseudotuberculosis O-antigen
Ye O:8
gene cluster
adk
hemH
What about Y. pestis?

08/11/2011
30.3.1996
gsk
~20 kb, 30.3.1996 !!!!

62
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
63
The gene clusters

Repeats
Y. pseudotuberculosis O:1b
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
Y. pestis
Repeats
08/11/2011
64
Y. pstb O:1b O-antigen structure

and biosynthesis
manA
Paratose
wecA
1,3
1,2
1,4
Mannose
1,3
Mannose
1,3
L-Fucose
1,2
GlcNAcn
08/11/2011
glmS
glmU
65
Y. pestis O-antigen cluster defects
Paratose
1,3
1,2
1,4
Mannose
1,3
Mannose
1,3
L-Fucose
1,2
GlcNAcn
08/11/2011
66
The mutations
CDP-Paratose biosynthesis
1-2 bp insertions in ddhB of Y.pestis
...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
08/11/2011
67
The mutations
O-antigen polymerase
1 bp insertion in wzy of Y.pestis
... 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
08/11/2011
68
The mutations
Paratosyltransferase
62 bp deletion in wbyI of Y.pestis
... 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
Short range homologous recombination
08/11/2011
69
The mutations
Fucose
1 bp insertion in gmd of Y.pestis
...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 deletion in fcl 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
08/11/2011
70
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
71
O:1b vs. Y.pestis

Intergenic repeats
21-77 bp insertions = 3-11 extra copies
of ATTTGCT in Y. pestis strains
3 repeats in O:1b
... Fcl
H Q N N F R K *
CATCAGAATAACTTCAGAAAATAGTTTC ....... ....... ....... ....... ....... ....... ....... ....... ....... .......
||||||||||||||||||||||||||||
CATCAGAATAACTTCAGAAAATAGTTTC ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT ATTTGCT
||||||||||||||||||||||||||||
||||||| |||||||
CATCAGAATAACTTCAGAAAATAGTTTC ....... ....... ....... ....... ....... ....... ....... ....... ATTTGCT ATTTGCT
14 repeats in EV76
08/11/2011
....... ATTTGCT
|||||||
ATTTGCT ATTTGCT
||||||| |||||||
ATTTGCT ATTTGCT
ATTTGCT
|||||||
ATTTGCT
|||||||
ATTTGCT
ATTTGCT
|||||||
ATTTGCT
|||||||
ATTTGCT
ATTTGGATATGGCG 15524 O:1b

||||||||||||||
ATTTGGATATGGCG EV76
||||||||||||||
ATTTGGATATGGCG CO 92
6 repeats in CO92
72
Evolution of
Y. pestis
Genomic maximum parsimony

tree and divergence dates based
on 1,364 non-repetitive, nonhomoplastic SNPs from 3,349
coding sequences in 16 Y. pestis
genomes .
08/11/2011
73
Anja Siitonen
Mark Achtman et al.
Hiroshi Fukushima
Elisabeth Carniel
Hannu Korkeala
Leila Sihvonen
Susanna Toivonen
Riikka Laukkanen-Ninios
11/8/2011
Thank You!
74

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Mikael Skurnik

2002Full professor of Bacteriology (University of Helsinki, Finland)

Black Death versus discomfort in

Three pathogenic species for humans and animals

Y. pseudotuberculosis and Y. enterocolitica -

Mikael Skurnik / Haartman Institute / University of Helsinki

Yersiniae make a good

Taxonomy and History

bacille de la tuberculose zooglique

Taxonomy and History

Y. enterocolitica was described in 1939 by

Like other Enterobacteriaceae

Y. enterocolitica and Y. pseudotuberculosis are gramnegative, aero-anaerobic rods

Properties that distinguish them

Motile only at temperatures <30 C

Taxonomy and History

Y. enterocolitica turned out to be

in addition to Y. enterocolitica sensu stricto

Taxonomy and History

Taxonomy and History

An important fish pathogen responsible for

Y. pseudotuberculosis infects a wider range of

Both are transmitted by the oral route

Y. enterocolitica is the most distantly

Y. pestis and Y. pseudotuberculosis

Not accepted for practical reasons

Relatedness at DNA level

History of bubonic plague

gradually spread to other

History of bubonic plague

The Black Death

3rd pandemic of plague

Started late in the 19th century in Far East

1894 came to Kanton and Hong-Kong

Small epidemics until 1950

the plague bacillus isolated in Hong-Kong

Improved hygienic conditions

Zoonosis mainly in rodents

Man does not have importance to the long

blood meal of fleas carry the

A 0.03 - 0.5 l blood meal from the rat

~300 bacteria or more

Hungry flea tries to eat repeatedly

PMN phagocytose and kill most bacteria

Bacteria survive and grow in monocytes

From the initial infection site bacteria move to

spread to liver and spleen

strong growth in blood, liver and

the circle closes

Buboes and skin are dark in

endotoxin induced TNF mediated

Endotoxic shock final

Genomic maximum parsimony

Helsinki ABS - December 17, 2007

MLST analysis of Y. pstb

Laukkanen-Ninios et al. Environmental Microbiology 2011.

417 Y. pstb strains included

A wide variety of ecological niches may

the environment (soil, water)

a wide range of animals

domestic (cat, dog)

The ability of Yersinia to multiply at 4 C is an important

A low number of pathogenic Y. enterocolitica in food may not