pPst

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pPst

• 9.5 kb- smallest plasmid
• Found only in Y. Pestis
• Encodes for plasminogen activator (pla)
• Cell surface protease
• Has coagulase activity evident only at
  temperatures below 30C, which initiates blockage
  in flea and forms fibrin matrix that anchors
  bacteria to proventiculus of flea
• At 37C exhibit fibronolytic activities, lyses
  fibrin at bite site and allows dissemination of
  bacterium

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pPst

• 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)

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pCD1

• 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
• Low Calcium response V antigen-LcrV
• Yersinia Outer membrane proteins- Yops
• Specific Yop chaperones- Syc
• Yop secretion proteins/Type III secretion system-
  Ysc

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pCD1LcrV/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 hosts immune response

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pCD1Yop 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

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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 family-downregulating
  TNF-?

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More Yops

• Yop O/YpkA
• Ser/Thr kinase that probably interferes with
  signaling pathways
• Yop M
• Prevents thrombin platelet aggregation
• Mutes inflammatory response by sequestering
  thrombin
• Yop B and D
• Translocate effectors across cell membrane

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Yops RegulationTemperature and Ca2

• When placed in 37C 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.

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pCD1Syc 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

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pCD1Ysc/ 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).

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Ysc/Type III secretion system
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Yersinias Deadly Kiss
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All Together Now!
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Clinical AspectsFocus on Bubonic Plague
Signs and symptoms Complications Differential
Diagnosis Diagnosis Treatment Prognosis Prevention
Vaccine Development
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Presenting Plague Patients

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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
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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 lt10 of cases
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Complications
2? Septicemic Plague due to hematogenous spread
(23 of patients)
- Purpuric Lesions - Acral Necrosis - DIC
disseminated intravascular
coagulation - Convulsions - Shock
Purpuric lesions
diffuse, hemorrhagic changes in skin (darkened
skin changes "black death)
Acral necrosis
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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 (lt 5) Death
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Distinguishing 1? from 2? Pneumonic Plague
no buboes 1-3 day incubation period
infectious pneumonitis from onset of
symptoms sputum production common less
severe evidence of disease in organs other
than lungs ? bacteria in alveoli
tracheal bronchial mucosal hemorrhages can
lead to 2? Septicemic Plague
symptoms
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
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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) DICConvulsions Shock
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Differential Diagnosis
Bubonic Plague
Chancroid Primary genital herpes 1? or 2?
syphilis Strangulated inguinal hernias
Streptococcal or staphylococcal adenitis
Tularemia Cat scratch disease Mycobacterial
infection Lymphogranuloma venereum