PATHOGENS

• The causative organism of pneumocystis pneumonia (PCP) is the fungus called Pneumocystis jirovecii.
  • The closest relative is Taphrina deformans, a fungal pathogen of peach trees.
• There are multiple species within the genus Pneumocystis
  • P. jirovecii (formerly identified as P. carinii and pronounced "yee row vet zee”) is a cause of disease in humans.
  • P. carinii and P. wakefieldiae infect rats, and P. murina infects mice.
    • Other species infect a range of animals (e.g., rabbits, sheep, monkeys, aquatic mammals).
• Morphological forms:
  • Trophic form:
    • Predominant forms (>90% in the lungs), multiply through binary fission, heterogeneous in shape, about ∼2 µm at greatest diameter, have a cell membrane and a fragile (not rigid) cell wall.
  • Asci or spore form (also called cyst):
    • Formed by conjugation of 2 opposite mating type trophic forms (sexual reproduction), more uniform in shape, about 8–10 µm in greatest diameter.
    • A rigid cell wall is essential for protecting the organism from environmental conditions outside the host (during airborne transmission), and it contains beta-glucans.
    • Mature cysts contain 8 intracystic bodies, which can be released to become trophic forms.
• Important biochemical properties:
  • Cell membrane lacks ergosterol; hence, antifungal agents such as azoles and amphotericin B products are inactive against Pneumocystis.
  • The fungus must synthesize its folic acid, a typical target for treatment (e.g., TMP/SMX).
  • Cyst cell walls contain beta-glucans, which can be helpful for diagnosis and perhaps treatment.
• Ecological niches and transmission
  
  • Specific environmental reservoirs are not well understood.
  • The organism grows well on epithelial cells within alveoli, and fungal burden correlates with immune dysfunction.
  • P. jiroveci may be present at low levels in healthy humans, which may serve as a transmission source.
  • Transmission is via airborne asci (cyst) forms passed from person to person.
  • There is constant inhalation and acquisition (transient or long-term) of the organism. Clinical disease may be due to new acquisition of the fungus by a susceptible patient or from the transformation of long-term carriage into active disease.