Download Y. Pestis

pPst
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9.5 kb- smallest plasmid

Found only in Y. Pestis
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Encodes for plasminogen activator (pla)
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Cell surface protease

Has coagulase activity evident only at temperatures
below 30°C, which initiates blockage in flea and forms
fibrin matrix that anchors bacteria to proventiculus of
flea

At 37°C exhibit fibronolytic activities, lyses fibrin at bite
site and allows dissemination of bacterium
pPst
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Other possible functions of Plasminogen
activator

Produces excess plasmin that causes ineffective
structures between inflammatory cells and fibrin

Reduces chemoattractants at the infection site
possibly via inhibition of IL-8.
Encodes bacteriosin pesticin (pst) and its
immunity protein (pim)
pCD1
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68-75 kb (depending on the strain)

Responsible for encoding anti-host genome

Y.Pestis, Y.pseudotuberculosis, and Y. Enterocolitis both
possess this plasmid

Encodes the Low Calcium Response System (LCRS)controlled by Temperature and Calcium concentration
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Low Calcium response V antigen-LcrV
Yersinia Outer membrane proteins- Yops
Specific Yop chaperones- Syc
Yop secretion proteins/Type III secretion system- Ysc
pCD1
LcrV/V antigen

LcrV protein plays a role in regulating the LCRS

It is a protective antigen that is associated with
resistance to phagocytosis

May play an immunosuppressive role, by inhibiting
cytokine production

Induces IL-10 production by macrophages this
downregulates host’s immune response
pCD1
Yop proteins

Altogether there are 29 Yop proteins

Yop effector proteins protect Y.pestis from
macrophages by destroying phagocytic signaling
capabilities

There are 6 Yops which directly or indirectly cause
disease:
 Yop E, Yop H, Yop J, Yop O, Yop M, Yop B and D
How Yops Thwart
Host Immune System
■ Yop E
■ Indirectly depolymerizes actin
microfilaments
■ Yop H
■ a protein tyrosine
phosphatase capable of
dephosphorylating host
proteins such as p125FAK and
p130Ca at focal adhesions,
inhibiting signal transduction
necessary for phagocytosis
■ Yop J
■ Binds to MAP kinase familydownregulating TNF-
More Yops

Yop O/YpkA
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Yop M

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Ser/Thr kinase that
probably interferes with
signaling pathways
Prevents thrombin platelet
aggregation
Mutes inflammatory
response by sequestering
thrombin
Yop B and D

Translocate effectors
across cell membrane
Yops Regulation
Temperature and Ca2+

When placed in 37°C and in a medium deprived of Ca2+,
Y. Pestis ceases growth and expression of Yops is
induced.

Yops expression and secretion is induced in Ca2+containing media by a local signal that occurs at the site
of contact between the pathogen and the eukaryotic cell.
This leads to the polarized transfer of at least five Yops
into the target cell.
pCD1
Syc proteins

Small Yop binding proteins

Not all Yops are syc associated

Act as chaperones by preventing Yop degradation

Act as “secretion pilots” leading the Yops to their location
of secretion
pCD1
Ysc/ Type III secretion system

Yops is mediated by Type III secretion
system called Ysc

Ysc Type III secretion system consists
of:

the core Ysc mechanism for secretion
through the two bacterial membranes

a delivery apparatus (YopB, YopD,
YopK, LcrV)

control elements (LcrE also called
YopN and TyeA at the surface and
LcrG in the cytosol)

anti-host effector proteins (YopE,
YopH, YopM, YpkA and YopJ).
Ysc/Type III secretion system
Yersinia’s Deadly Kiss
All Together Now!
Clinical Aspects
Focus on Bubonic Plague
Signs and symptoms
Complications
Differential Diagnosis
Diagnosis
Treatment
Prognosis
Prevention
Vaccine Development
Presenting Plague Patients
%
Signs & Symptoms
Within 2-7 days of Infection:
■ Severe malaise or prostration ---75%
■ High fever, headache ---20%-85%
■ Chills --- 40%
■ Vomiting ---25%-49%
■ Altered mentation ---26%-38%
■ Abdominal pain --- 18%
■ Other: bladder distention, apathy, confusion, fright, anxiety, oliguria,
anuria, tachycardia, hypotension, leukocytosis
Signs & Symptoms
6-8 hours following onset of
symptoms:
■ Pain/tenderness at regional lymph nodes
enlarge to be called buboes
- extremely painful
- occur in groin*, axilla or cervical areas
- usually occur in 1 region, but multiple can
be seen
- may drain pus if left untreated
■ ulcer or skin lesions at site of flea bite
<10% of cases
Complications
■ 2 Septicemic Plague due to hematogenous spread
(23% of patients)
- Purpuric Lesions
- Acral Necrosis
- DIC
disseminated
intravascular
coagulation
Purpuric lesions
diffuse, hemorrhagic
changes in skin
(darkened skin changes
="black death”)
- Convulsions
Acral necrosis
- Shock
Complications
■ 2 Pneumonic Plague (5-15% of patients)
- begins as interstitial pneumonitis;  bacteria in interstitium
- show signs and symptoms prior to developing advanced
pneumonitis:
High fever
Severe bronchopneumonia
Chest pain
Coughing or spitting up blood
Difficulty breathing
■ Infection of Buboes
■ Meningitis (< 5%)
■ Death
Distinguishing 1 from 2
Pneumonic Plague
■ no buboes
symptoms
■ 1-3 day incubation period
■ infectious pneumonitis from onset of
symptoms
■ sputum production common
■ less severe evidence of disease
in organs other than lungs
Sudden onset of fever, chills,
headache, body pains, weakness,
chest discomfort & tightness;
Coughing with sputum production;
Difficulty breathing; Coughing or
spitting up blood; GI symptoms;
Pharyngitis
■  bacteria in alveoli
■ tracheal & bronchial mucosal hemorrhages
■ can lead to 2 Septicemic Plague
Distinguishing 1 from 2
Septicemic Plague
■ no buboes
■ 1-4 day incubation period
■ more GI symptoms
■ can also lead to 2 Pneumonic
Plague (25%)
■ meningitis is 4x more common
symptoms
Fever and chills
Extreme exhaustion
Bleeding disorder
Necrosis of small vessels
Hemorrhagic Skin lesions
(purpuric lesions, acral necrosis)
Gangrene of extremities (nose or digits)
DIC
Convulsions
Shock
Differential Diagnosis
Bubonic Plague
■ Streptococcal or
staphylococcal adenitis
■ Tularemia
■ Cat scratch disease
■ Mycobacterial infection
■ Lymphogranuloma
venereum
■ Chancroid
■ Primary genital herpes
■ 1 or 2 syphilis
■ Strangulated inguinal
hernias