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: C. pneumoniae:

bronchitis which causes pneumonia, which causes pneumonia, pharyngitis,

• • •

Laboratory Diagnosis and Treatment

C. trachomatis i

s 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

tetracyclines of

Chlamydia

includes macrolides and

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.