Lecture 9 - Chlamydia Flashcards
What are two genera
Chlamydia - c.trochomatis - human pathogens
Chlamydophila - contain two human pathogens c.psittaci (birds), c.pneumoniae (if think have cold or flu may have infection)
What does c abortus do
Case spontaneous in sheep
Name some strand characteristics that chlamydia have that make it more virus like
No peptidoglycan
Cannot be filtered by 0.45um filter (most bacteria 1um in length)
Contain both DNA and RNA
Own ribosomes very unlike virus
Make own proteins, nucleus acid and lipids ( nt reading upon cell)
Possess inner and outer membrane
MUST LIVE WITHIN CELL TO SURVIVE
What is strange that doesnt have peptidoglycan
Has machinery to make it but doesn’t have it
Does chylamida have LPS or LOS
LOS
Desrcribe the life cycle of chyladia
BIPHASIC
Extracellular form and intracellular form
Describe extracellular form and compare to intracellular
E - have elementary body EB whereas Intra has reticulate body (RB)
E is small whereas I is larger
E 0.1-0.3 I- 1um
E - no metabolism I - Metbaolically active
E - highly resistant, non replicating. I - Senstiive, replicating.
E - spore like I - fragile
Why does it not matter is RB is sensitive
Live in cell at this tim - nice environment
How do chlamydia replicate
Binary fission
Describe life cycle part 1
EB bind cell
Be contained and survive within phagosome vesicles as RB. Divide inside vesicle (called inclusion)
Life cycle part 2 (back to EB)
Reorganised into EB
Inclusion contain EB and RB
COntinued reorganisation
Extrusion of mass of EB by reverse endocytosis
Describe lifecycle in hours from EB to EB release
3hrs have EB in cell. Organism need to condense DNA to replicate
At 9hrs organism dividing
15 hrs Incluson body got bigger and lots of membrane. Organism need membrane to expand inclusion as organism keep dividing
40 hrs fewer RB more EB some intermediate bodies start to condense dna so can EB again
Lytic release - burst cell open like lytic viruses
Describe inclusion of c trochomatis
Phagosome fuse to make one large inclusion (lots of membrane )
Stain with iodine see huge spot (incluson body full of it)
How many genes does chlamydia have
600 genes, approx 1/4 of ecoli
Parasitic so dont need big genome
Require host for energy - energy parasites . Nutrients
What is interesting about LPS of chlamydia
SMALLEST NAUTRALLY OCCURING LPS
Only lipid A anchor and key sugars - same to family so use antibodies to identify all chlamydia as all have sameebdotoxin
Why do we not know a lot about structure of chlamydia
Need to see condensed form to replicating form
What OMP do for chla
Form porin - allow it to get what it needs from cell
Variability or protection so antibodies may not be able to bind and protect as MOMP Aldo on infectious form
What gives structure to c tromachtic
Cysteine rich - disulphides bridges - no need or peptidoglycan
Why is typical suggestion for why something is hugely variable
Immune evasion
What are inc proteins
In inclusion membranes - allow us to do nutrition and parasitising. Also immune evasion - preevent lysosomes fusing with phagosome - avoid killing
RB SPECIFIC
What is a biovar
Biological varient - behave different biologically
Trachoma
Lymphogranuloma (LGV)
What is serovar
Based on MOMP
Variation of serum so different antibody response
Use antibody to bind to organisms and differentiate them.
E..g antibody 1 bind to this serovar etc
15 and 4 are serovars
What are biological features of two biovars of c trochomatis
Trochoma - serovar 15 -
- Relatively non invasive
Lymphogranuloma venereum (LGV) - serovar 4- CAUSE SYSTEMIC EFFECTS
What is target for c trochomatis biovars
Mucosal epitheliaum for both
What little do we know about chylamdial infection mechanisms
Efficient
No efinitive host cell receptor - use GAG complex sugars coming off proteins called heparan sulphates e.g. CD44 on HUMAN CELLS
We know MOMP on bacterial cell has some role of adhesion.
Use cytoskeleton to be uptaken
Different uptake mechanism for each chylamdia
Why is persisting form troublesome
- inhibit lysosome fusion
- inhibit cell death mechanisms. Just sit inside cell not replicating.
AS NOT REPLICATING ANTIBIOTICS NEED ORGANISM TO REPLICATE TO DESTROY IT.
Where can you find infections of chlamydia and what are 2 key presentations
- urethra Cervix Endometrium Fallopian, Anorectum Respiratory tract Conjunctiva
Present via inflammation and cell death
How is pathogenesis of chlamydia an issue
Relatively uncontrolled inflammation
Cytokines from LOS
Infiltration of nueutrohils and other immune cells
Try to prevent fibrosis from chronic inflammation - loss of tissue function. Can also get necrosis
What are the serovars and their associated disease
A,B,Ba,C - trachoma - eye infection
D-K - GU (genital urinary) tract disease
L1,L2,L2a,L2b,L3 - lymphogranuloma venereum
How are serovars D-k Spread
Spread by sexual contact
- vaginal intercourse
- anal sex
- less commonly oral sex
For male GTI - urethritis
If discharge is yellow gonococcal NGU - non gonoccos like urethritis - if discharge grey/white especially in the morning Dysuria - pain on urination (NGU) Less purulent than gonococcal 7-14 dy incubation period
Describe epididymitis infection
Relatively non specific presentation
Testicular pain, masses, inflammation
Can lead to obstruction of sperm collecting tubes and VERY rearley infetility
Formal confirmation required. Symptoms not enough to diagnose
IN female reproductive tract infections
Harbour ascending infections better than men - route to other big organs - cervicitis - cervical inflammation - dysuria Soreness Discharge Asymptomatic (primarily)
Serovars D-K (especially E)
Can get urethritis - less common in women
Describe pelvic inflammatory disease
Infection of uterus, fallopian tubes and adjacent pelvic structures
Ascending infection
Inflammation of uterine lining (endometritis) S F fallopian tubes (salpingitis)
Can go from asymptomatic to sever salpingitis
Tubul blockage and infertility
As LGv is more invasive, as well as Mucosa what else does it efffect
Secondary lymphoid tissues - inflammation of lymph nodes - stop fluid drainin due to blockage so swell up as buboes and ultimately elephantiasis
What does it mean if people are asymptomatic
Sexually active reservoir of infection
Women often diagnosed from partner check from boyfriend
How many mil new cases are in us each year
1.5 mil 2011
8% increase on 2010 estimated actually 4+ million
Peak incidence later teens early 20s
Where is LGV on increase
US and Europe
What defences are there for chlamydia
Innate and adaptive - not enough to clear it. Persist in body
Will get antibodies but will not protect from repeat infection - can be common. Get IgA and IgG and IgM,
Cell mediated immunity - T cell CD8 Tc - some protection
IFNy - see other flashcard for more info
What is main defence against chla
CONTROL BUT NOT CLEAR
Indoleamine 2,3-dioxygenase - break down tryptophan - so bacteria cannot use it to
Nitric oxide synthase anther defence, catabolise arginine to create nitrous oxide (iNOS)
Can also decrease transferrin receptor (iron limitation)
How does chlamydia evade
Hide in cell. - antibodies and complement not touch bacteria
Down regulate MHC class I Inhibit phagolysosome fusion
CAN INFECT MACROPHAGES - induce apoptosis of T cells - reduced cell mediated immunity.
Get arthritis or athersclerosis - due to chalamydia being hidden in macs and been delivered there
What are risk factors for infections (also how it diagnosed)
Lots of partners Unprpotected sex Age of patient <25) Sexual activity Numbers of partners
Diagnose via above and taking a sample
What are tests that can be used to diagnose
Sampling affected area - swabs. BUT can drive infection further
To detect:
- culture - isolation and growth in lab, ID of inclusions but relatively insensitive
- can use antibodies against EB’s - good for eye infections (flourescent)
- can use ELISA - look for antibodies present - challenge is may have antibodies because have respiratory infection - wont tell you what route we get infection.
- PCR!!!!! THIS METHOD IS USED AS SENSITIVE, SPECFIC, FEW FALSE POSTIVE.
WHAT THERAPIES ARE AVAILABLE
EASY TO TREAT:
Genital infection - oral tetracycline or doxycycline - course of antibiotics
OR single dose azithromycin (ensures compliance - need to abstain from sex for seven days and finish course of antibiotics)
HARDER TO TREAT - CHRONIC DISEASES E.G. PELVIC INFLAMMATORY DISEASE - PID) as dependant on compliance.
- need intravascular and intramuscular injections of antibiotics
- compound therapy - multiple antibiotics for long periods of time.
- clindamycin (i.v) plus gentamicin (i.v./i.m.)
- Cefotoxitin (i.v.) + doxycycline (oral/i.v.)
What is management and protection for chlamydia
Partner check - essential given high rate of asymptomatic carriers
Prevention - abstinence, especially when receiving treatments, barrier protection.
Points to remember
Most bacterial infection of reproductive tract are STDs
Most affect women
Women suffer most
Theres no effective female controlled barrier - more on males - take power away from women
