OBLIGATE INTRACELLULAR PARASITES CHARACTERISTICS · Family = chlamydiaceae, genus = chlamydia . Virus-like in that they need to be in cells in order to survive (take energy and nutrients) · Lack peptidoglycan · Cannot be filtered by 0.45um filter (as small as viruses) · Contains DNA and RNA - very small genome <1000kb, 600 genes (some even smaller due to natural selection from PCR use) · Possess ribosomes . Make their own proteins, nucleic acids and lipids · Possess inner and outer membranes · Classic gram -ive structure - lipooligosaccharide (LOS)(poor endotoxin activity but lipid A and core) · Unique lifecycle THE LIFECYCLE OF CHLAMYDIACEAE 1. Susceptible cell 2. Ingestion of the EB by phagosome 3. Reorganisation into RB inside the phagosome 4. Growth by binary fission 5. Some reorganised into EBs so inclusion contains a mixture 6. Continued reorganisation until extrusion of mass of EBs by reverse endocytosis ~ 48-72hrs · C. trachomatis = phagosome fuse to make one large inclusion Elementary Body - Extracellular Form Reticulate Body - Intracellular Form Small (0.1-0.3um) No metabolism Metabolically active Highly resistant, non-replicating Sensitive, replicating Spore-like Fragile Dense Less dense - dappling Larger (1um +) C. TRACHOMATIS Cell Membrane Structure · OMPs (outer membrane proteins) · OMP1 / MOMP · 40kDa trimer, porin function · Unique to each species · Abs to variable segments (VS1-4) can neutralise infectivity · Defines serological variants (antibody responses helps define different subclasses) · OMP2 · 60kDa cysteine-rich PROTEIN · Gives structural stability in EB (don't have peptidoglycan) · POMPs (polymorphic OMPs) · 90kDa EB surface protein · Immune evasion? · Inc proteins · RB specific · Fusion of inclusion membranes · Nutrition?
Biovar · Immune evasion? Trachoma Serovar (based on MOMP) Biological Features Non-invasive Target Mucosal epithelium 15 Lymphogranuloma Venereum (LGV) 4 Systemic effects Mucosal epithelial THE INFECTION AND PATHOGENIC PROCESSES OF CHLAMYDIA The Infection · Efficient · No definitive host cell receptor - GAG or heparan sulphate . No definitive bacterial adhesion - GAG or MOMP · Not all chlamydia use the same mechanism . Key events = inhibition of lysosome fusion and inhibition of host cell death . Only infect epithelial cells of mucous membranes but these appear in many places in the body (ie. urethra, cervix, endometrium, fallopian tubes, anorectum, respiratory tract, conjunctiva) · Presentation of infection = cell destruction and inflammation (cytokines from infected cell which are LOS dependent and infiltration of neutrophils, lymphocytes, macrophages, plasma cells and eosinophils · Infection untreated = chronic inflammation, necrosis, scarring and fibrosis CLINICAL CONDITIONS Serovars D-K · Male Reproductive Tract Infections · Urethritis: · NGU (non-gonococcal) = white/grey discharge from penis, less purulent (less pus) · Epididymitis: · Testicular pain, masses, inflammation = non-specific presentation · Can lead to obstruction of sperm collecting tubes and infertility · Formal diagnosis required · Female Reproductive Tract Infections · Urethritis · Cervicitis: · Dysuria · Soreness · Discharge · Asymptomatic · Pelvic inflammatory disease · Infection of uterus, fallopian tubes and adjacent pelvic structures · Ascending infection ·