Chlamydia Flashcards
Show a phylogenetic overview of bacteria and where Chlamydia sp. fits in
State the order, family, genus and species of Chlamydia
Order- Chlamydiales
Family-Chlamydiaceae
Genus- Chlamydia
Species-C. trachomatis
How many species of chalmydia cause human infections?
Three species cause human infections
Others cause animal infections & zoonoses
What are the characteristics of Chlamydia?
- Lack peptidoglycan
- Cannot be filtered by 0.45µm filter
- Contain BOTH DNA and RNA
- Possess ribosomes
- Make their own proteins, nucleic acids and lipids
- Possess inner and outer membranes
- Unique bacterial life cycle
What are the characteristics of chlamydias membrane?
Gram negative
Typical membrane structure
Bi-phasic life cycle: Extracellular form
- EB – Elementary body
- Small
- 0.1-0.3µm
- No metabolism
- Highly resistant
- Non-replicating
- Spore-like
Bi-phasic life cycle: Intracellular form
- RB – Reticulate Body
- Larger
- 1µm
- Metabolically ACTIVE
- Sensitive
- Replicating
- Fragile
Produce an image of Bi-phasic life cycle
Infection ‘Life’ Cycle – key events
- Infectiouse elementary body (EB) attaches and enters
- Phagosome formes
- EB to reticulate body (RB) differentiation
- Endosome forms
- RB multiplication
- RB to EB differentiation
- Inclusion maturation
- Inclusion exocytosis
- EBs released
Describe the Growth cycle
Phagosome fuses with intracellular membranes
- Including golgi
C. trachomatis
- Phagosome fuse to make one large INCLUSION
What are the characteristics of Chlamydia?
–Very small genome (<1000 kb) 25% of E. coli
–ca 600 genes
What does chlamydia require a host for?
–Energy
•Energy parasites
–Nutrients
Chlamydia – Endotoxin (LOS)
- LipoOLIGOsaccharide
- Common to all family members
- Poor endotoxin activity
–Lipid A
–Core
•Smallest naturally occurring
C. trachomatis structure: – OMP1/MOMP
- 40kDa trimer; porin function
- Unique to each species
- Abs to variable segments (VS1-4) can neutralise infectivity
- Defines serological variants
C. trachomatis structure: OMP2
- 60kDa Cysteine-rich protein
- Structural stability in EB
C. trachomatis structure: POMPs (polymorphic OMPs)
- 90kDa EB surface protein
- Immune evasion?
C. trachomatis structure: Inc proteins
–RB specific
–Fusion of inclusion membranes
- nutrition?
- Immune evasion?
Describe a Chlamydial Infection
- Efficient
- Poorly understood
–Microfilament-dependent phagocytosis
–Receptor-mediated endocytosis
•No definitive host cell receptor
–GAG; heparan sulphate
•No definitive bacterial adhesin
–GAG; MOMP
Not all Chlamydia use the same mechanism
C. trachomatis biovars & serovars
Biovar→Trachoma
Serovar (based on MOMP)→15
Biological features→Rel. non-invasive
Target→Mucosal epithelium
Biovar→ Lymphogranuloma venereum (LGV)
Serovar (based on MOMP)→ 4
Biological features→Can cause systemic effects
Target→Mucosal epithelium
Infections
•Limited target cell range
•Epithelial cells of mucous membranes
–Urethra
–Cervix
–Endometrium
–Fallopian tubes
–Anorectum
–Respiratory tract
–Conjunctiva
•Presentation
–Cell destruction
–Inflammation
Pathogenesis: How does Infection lead to inflammation?
–cytokines from infected cells (LOS-dependent)
–Infiltration of
- NØ (Limited)
- lymphocytes, macrophages, plasma cells, eosinophils
If untreated or not cleared, infection can lead to:
–chronic inflammation
–necrosis
–scarring & fibrosis
What are the clinical conditions?
Serovars:
- A, B, Ba, C
- D-K
- L1, L2, L2a, L2b, L3
Disease
- Trachoma
- GU tract disease
- Lymphogranuloma venereum
Infections Serovars D-K: How are they spread?
•Spread by sexual contact
–vaginal intercourse
–anal sex
–less commonly oral sex
•Spread during birth
–Infected mother transmission to non-infected neonate
Male GTIs - urethritis
- NGU - non-gonococcal
- 7-14 day incubation period
- Dysuria, white/grey discharge (esp. AM)
- Less purulent than Gonococcal
Epididymitis
- Relatively non-specific presentation
- Testicular pain, masses, inflammation
- Can lead to obstruction of sperm collecting tubes and infertility
- Formal diagnosis required
Name Female Reproductive tract infections
- Lower GT is prime chlamydial target
- Cervicitis
–Dysuria
–Soreness
–Discharge
–Asymptomatic
- Serovars D-K (esp. E)
- Urethritis
- Ascending infections
Describe Pelvic Inflammatory Disease
- Infection of uterus, fallopian tubes and adjacent pelvic structures
- Ascending infection
- Inflammation of uterine lining (endometritis) & fallopian tubes (salpingitis)
- Asymptomatic ó severe salpingitis
- Tubal blockage and infertility
Describe Infections LGV
•Lymphogranuloma venereum biovar
–Serovars L1, L2, L2a and L3
•Causes systemic effects
–Lymphadenopathy
–Inguinal buboes
–Elephantiasis
•Rel scarce STD
Describe C. trachomatis epidemiology
•Infections can be asymptomatic in a majority of cases
–Varied estimates
•Can lead to
–Sexually active reservoir of infection
•Women are more often asymptomatic
–Often diagnosed after attending clinic with partner
C. trachomatis epidemiology stats
•Most common sexually transmitted bacterial pathogen
–D-K
•2017 in US
–1.7 million new cases (500 cases per 100,000)
–Underestimate (prob 4+ million) and rising!
- 200,228 new UK cases in 2014 (46% of all STI in UK)
- Peak incidence - late teens – early 20s
- LGV - on the increase in US and Europe
C. trachomatis epidemiology – US 2017 data
Explain the Hosts defence
•Innate & Adaptive
–insufficient for clearance
–-> persistence
•Abs
–IgA, G, M BUT no lasting protection
•Cell-mediated immunity
–CD8 Tc exert some protection
•IFN-γ
–indoleamine 2,3-dioxygenase
–iNOS
–decrease transferrin receptor (iron limitation)
Describe Host defence - evasion
•Intracellular growth
–protects from Ab & complement
•Down-regulation of MHC I
•Inhibition
–phagolysosome fusion
–Apoptosis of host cell
•Chlamydia can infect MØ
–induce apoptosis in T cells
•reduced cell-mediated immunity
Diagnosis: Likelihood of infection
•Likelihood of infection
–consider symptoms
–age of patient (<25)
–sexual activity
–numbers of partners
•Sampling
Diagnosis: Sampling affected area, Culture, Immuno-fluorescence, Enzyme Immuno-Assay, NAATs
•Sampling affected area
–Do no harm (endometrial swabs may carry infection higher)
–Non-invasive methods preferred (esp. in men) though not always suitable
•Culture
–Isolation & growth in lab, ID of inclusions
–Highly specific, rel. insensitive
•Immuno-fluorescence
–test for anti-chlamydial Abs (usually against EBs)
•Enzyme Immuno-Assay
–Microplate peptide-based assays to measure anti-chlamydial Abs
•NAATs- nucleic acid amplification tests
–Sensitive, specific, few false positives (e.g.PCR)
Therapy
•Genital Infection
–Oral tetracycline or doxycycline
•course of antibiotics
–Single dose azithromycin
•ensures compliance
•Complicated infections (e.g. PID)
–Compound, multi-dose therapy
- Clindamycin (i.v.) plus gentamicin (i.v./i.m.)
- Cefoxitin (i.v.) + doxycycline (oral/i.v.)
Management & Prevention
•Partner check
–essential given high rate of asymptomatic carriers
•Prevention
–Abstinence
•Especially whilst receiving treatment
–Barrier protection
Remember
- Most bacterial infections of reproductive tract are STDs
- Most often affects women
- Women suffer most
- There’s no effective female-controlled barrier
