Transcript Obligate Intracellular Organisms

Obligate Intracellular Organisms
Bacterial Intracellular Organisms
Pathogenesis not well
understood. Adheres
to endothelial cells
and is engulfed
•Bartonella
spp
Lives in a phagosome &
prevents phagolysosomal
fusion
•Chlamydiae spp
•M. Tuberculosis
•Legionella spp
•Toxoplasma gondii
Intracellular
organism
Escapes from phagosome
& lives in cytosol
Lives in
phagolysosome
•Leishmenia
•Coxiella
•Ricketssiae
•Listeria
•shigella
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
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
Chlamydia Species
• Antigenic composition:
• Serotyping is based on specific cell wall
proteins
• Each serotype is associated with a specific
disease
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
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
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
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
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
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
Life Cycle
Pathogenicity
• Generally have animal
reservoirs
• Transmitted by the
bite of an arthropod
vector
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.
Clinical Disease
• Spotted fever
– Fever, headache
and rash
– Eschar = black scar
at site of bite
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.