Pseudomonas sp' Burkholderia sp'

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Pseudomonas sp.Burkholderia sp.
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General Characteristics

• Gram-negative
• require oxygen, other inorganic electron acceptor
• motile
• Widely distributed in soil and water, human gut
  (10)
• diverse metabolic capabilities
• many can grow in distilled water to gt106 per ml
• growth on wide range of carbon sources
• readily available for nosocomial infections
• Susceptible to drying, airborne spread less
  likely

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P. aeruginosa

• Disease rare in healthy individuals
• chronic external otitis
• Disease most common in those with
• natural immunologic deficiency
• immunosuppressive therapy
• burns
• chronic pulmonary disease (cystic fibrosis)
• IV narcotic use
• renal dialysis
• Most common sites of infection urinary tract,
  burns

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P. aeruginosa

• Septicemia, abscesses
• Corneal infections
• Meningitis
• Bronchopneumonia
• Subacute endocarditis

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Pathogenesis

• Deficiencies in colonization
• may explain opportunism
• can't accomplish first steps in pathogenesis
• Burns burned mouse model
• normal mouse LD50 188 cfu
• burned mouse LD50 30 cfu
• Lungs requires compromised lung (eg CF)
• rat model uses agar beads imbedded with bugs

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Pathogenesis

• Alginate (polysaccharide)
• viscous gel around bacteria
• coating may protect from phagocytosis in lung
  infections
• only produces septicemia in patients with
  neutropenia
• turned off in vitro, rapidly turned back on in
  vivo

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Exotoxin A

• AB toxin (11)
• Most clinical isolates, those without less
  virulent
• Binds to receptor, internalized
• Regulation by iron
• Similar in structure, function to diphtheria toxin

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Other Virulence Factors

• 90 pigmented
• common diagnostic feature
• involved in iron acquisition
• Pyocyanin
• antibacterial, aids colonization
• damages endothelial tissue in vitro
• formation of superoxide, peroxide
• Pyochelin mediates conversion of superoxide to
  hydroxyl
• Fluorescein flouresces in tissue

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Antibiotic Resistance

• Broadly resistant to antibiotics,
  plasmid-mediated
• Resistance mediated by loss of appropriate porins
  for entry
• Treatment often fails, mortality gt 80

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Burkholderia pseudomallei

• Causes melioidosis
• wound infection
• benign pulmonary disease
• rapidly fatal septicemia with disseminated
  abscesses
• Zoonosis
• occupational disease of veterinarians, horse
  caretakers, slaughterhouse employees
• endemic to Southeast Asia, Northern Territory of
  Australia significant number of cases in Vietnam
  vets
• Latency leads to recrudescence (up to 26 years)
• Infection by exposure to organism in soil and
  surface water

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Melioidosis, Tsunami-Related

• Positive culture from leg wound (man from
  Brisbane, Australia, on holiday in Sri Lanka,
  swept inland considerable distance bytsunami,
  sustained leg injury resulting in abscess
  formation)
• Sparse growth from surgically-treated Achilles
  tendon injury found after patient's return from
  Asia.
• Blood culture positive, wound isolation from two
  patients with pneumonia.

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Burkholderia mallei

• Glanders in horses, transmitted to man
• Rare in the West, usually found in Asia, Africa,
  Middle East
• Necrosis of nasal mucus membranes, lymphatics,
  lymph nodes, skin
• Also acute or chronic pneumonia

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BW threat agents?B. pseudomallei

• Conan-Doyle recognized bioweapon potential of B.
  pseudomallei
• Sherlock Holmes story "The Dying Detective."
• Holmes sent box designed to inoculate the
  recipient with "Tapanuli fever" (meliodiosis)
• Now considered important potential bioweapon
• overseas funding for research on virulence
  factors, vaccines
• former USSR
• US (pre1969)
• Egypt
• Potentially high mortality rate
• Intrinsic antibiotic resistance, wide host range

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BW threat agents?B. mallei

• Germany - German spies used glanders in the U.S.
  during WWI
• Japan evaluated glanders at Unit 731 during WWII
• US Fort Detrick
• Soviet Union - weaponized glanders during Cold
  War, used vs mujaheddin

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Liver and Spleen Abscesses
CT Scan
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Virulence factors

• Metalloprotease
• Lipase, phospholipase C, hemolysin
• Capsule