Obligate Intracellular Organisms

1
Obligate Intracellular Organisms
2
Bacterial Intracellular Organisms

• Bartonella
• spp

Pathogenesis not well understood. Adheres to
endothelial cells and is engulfed

• Chlamydiae spp
• M. Tuberculosis
• Legionella spp
• Toxoplasma gondii

Lives in a phagosome prevents phagolysosomal
fusion
Intracellular organism
Escapes from phagosome lives in cytosol

• Ricketssiae
• Listeria
• shigella

Lives in phagolysosome

• Leishmenia
• Coxiella

3
Chlamydia Species

• Obligate intracellular organisms
• Small round to ovoid cells, 0.3µm
• Cell has peptidoglycan and an outer lipid layer
  resembling that of a Gram negative bacteria
• Genome much smaller than that of other bacteria
• They cannot make ATP (adinosine triphosphate)
  dependent on host cell for energy production
• They import nutrients from the cytosol into the
  endosome with the help of tubular projections on
  the surface of the reticulate body

4
Chlamydia Species

• Growth characteristics cannot be grown on
  artificial bacteriologic medium, only grows
  within living tissue or tissue culture cells
• Replication is by binary fission but they undergo
  morphologic variation during replication cycle
• have distinct elementary bodies (EB) adapted for
  extracellular survival and initiation of
  infection and
• reproductive reticulate body (RB) forms for
  intracellular replication

5
Chlamydia Species

• Antigenic composition
• Serotyping is based on specific cell wall
  proteins
• Each serotype is associated with a specific
  disease

6
Epidemiology

• Chlamydiae are susceptible to environmental
  conditions, survive only a short time outside the
  host
• Transmission is by direct contact among humans
• C. psittaci is pathogenic for birds and domestic
  fowl and is transmitted to humans by inhalation
  of bacteria in droplets or dust

7
Pathogenicity

• Highly infectious
• Pathogenesis of disease caused by these bacteria
  is not well understood
• Different strains of both C. trachomatis and C.
  psittaci show different degrees of virulence
• Phagocytosed chlamydiae prevent fusion of
  lysosome to the phagosome thus escape
  intracellular destruction by lysosomal enzymes
• Produce heat-labile toxin
• Competition for nutrients
• C. trachomatis may exist in a latent state and
  may reactivate if host becomes immunosuppressed

8
Diseases caused by Chlamydia species

• Chlamydia cause persistent and recurrent
  infections
• Three species cause human disease 
• C. trachomatis trachoma a chronic infection
  which causes blindness , inclusion conjunctivitis
  an acute infection, urethritis, cervicitis,
  salpingitis and lymphogranuloma venerium (LGV)
• C psittaci which causes pneumonia,
• C. pneumoniae which causes pneumonia,
  pharyngitis, bronchitis

9
Laboratory Diagnosis and Treatment

• C. trachomatis is detected using
• Direct fluorescent antibody staining of genital
  exudates with fluorescein-labelled monoclonal
  antibodies against MOMP or LPS. 
• Serologic techniques are not used for C.
  trachomatis and culture is rarely done. 
• Nucleic acid hybridization techniques are widely
  used to detect asymptomatic genital infection in
  women.
• C. psittaci pneumonia a 4 fold rise in CF
  antibody to chlamydial group antigen
• Treatment of Chlamydia includes macrolides and
  tetracyclines

10
Rickettsia

• Obligate intracellular pathogens
• Small GNB 0.3-0.5µm
• Stain poorly with bacteriologic stains
• Visualized easily with Giemsa
• Important members include R. prowazekii, R.
  typhi, and R rickettsii

11
Growth characteristics

• Only grows within living tissue or tissue culture
  cells
• Intracellular growth enter host by endocytosis,
  produces a phospholipase which destroys the
  phagosome and it begins to grow in the cytoplasm
  of host cell.
• require coenzyme A, nicotinamide-adenine
  dinucleotide (NAD), energy from host cell
• Free rickettsiae cease metabolic activity and
  begin to leak intracellular constituents
  resulting in lack of infectivity within a short
  period

12
Life Cycle
13
Pathogenicity

• Generally have animal reservoirs
• Transmitted by the bite of an arthropod vector

14
Pathogenesis

• Bacteria invade the vascular epithelial cells and
  become widely disseminated
• Damage to the endothelial cells in small vessels
  causes vasculitis, obstruction, capillary leaks
  and thrombosis. 
• This causes a rash, organ damage and potentially
  shock.

15
Clinical Disease

• Spotted fever
• Fever, headache and rash
• Eschar black scar at site of bite

16
Diagnosis and Treatment

• By necessity, the diagnosis must be made
  clinically
• If a rickettsial illness is suspected, treat
  first with an antibiotic that can reach a
  therapeutic concentration inside infected cells
  (tetracyclines, long acting macrolides,
  fluoroquinolones etc.), and then confirm the
  diagnosis with serology.