chlamydia trachomatis
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A ppt on Chlamydia trachomatis, structure, life cycle and virulence factorsTRANSCRIPT
Chlamydia trachomatis:
Structure, Life cycle & Virulence factors
Mays Yousuf Ismail ©
Al-Quds UniversityJerusalem- Palestine Nov 2012
It’s Challenging !!
4-5 Million/yearPID: US$10 billion/year
> %90 pop. infected
> 500 Million @ high risk
6 Million are Blind
POVERTY
LIMITED ACCSESS TO WATER
PERSONAL HYGIENE
ECONOMY POVERTY A GLOBAL CRISIS !!
Throat infection
Trachoma
Cervicitis
What we already know about Chlamydia trachomatis !!
Aerobic, obligate intracellularparasite of eukaryotic cells
Questions raised from this cryptic fact!!
1. Why does it live only intracellularly?
2. Is it really a bacteria? Or a virus?
3. What are its morphology? And its Metabolism
pathways?
4. How does it cause disease?
5. What are its weak points?
6. Can we prevent its infection? Can we make a
vaccine?
What makes Chlamydia trachomatis UNIQUE; What
makes it CLEVER !!
Scientists discovered that Chlamydia trachomatis has a biphasic life cycle
Non-infectious, intracellular
reticulate bodies
Infectious extracellular
elementary bodies
3 hrs
20 hrs
30 – 72 hrs
7-21 days
Chlamydia trachomatis biphasic life cycle
But what makes EB infectious?? why isn’t it found intracellularly?
and What makes RB survive intracellularly? why isn’t it found extracellularly?
Elementary Body Reticulate Body
Extracellular form Intra-cytoplasmatic form
Infectious particle,
released when infected
cells rupture.
Non-infectious particle,
never released.
Analogous to a sporeWith iodine stain, appears
as cellular inclusions
0.25 to 0.3 μm in diameter 0.6 μm in diameter.
Presence of rigid cell wall No rigid cell wall; still,
membrane-bound
Preserves genome,
plasmids, RNA
polymerase,
and ribosomes.
All structures are retained
No Replication
Replication by binary
fission, rate of 2-3 hrs per
generation
Metabolically inactive Metabolically active
Can induce Exo-, and
Endo-cytosis
Can’t induce Exo-, and
Endo-cytosis
Hmmmm.. Let’s see …!!
So, now we know we’re not dealing with only one Bacterium it’s
TWO in ONE !!
And this maybe makes it easier ?!
**The fact that the Elementary body is found
extracellularly, and has a cell wall.
** Chlamydia has a unique cell wall; outer LPS membrane
but NO peptidoglycan.
Made it possible to use Gram Stain to figure out the
bacteria’s Morphology !!
Chlamydia trachomatis is a Gram-negative coccobacilli
bacteria.
**The fact that the Reticulate body is found intracellularly
as inclusions.
Made it possible to use Giemsa to detect it
intracellularly !!
Chlamydia trachomatis is as small or smaller than
many viruses; 0.25 to 1.5 μm.
Why does it live only intracellularly?
Although Chlamydia trachomatis has a Glycolytic
pathway, a linked tricarboxylic acid cycle and an
electron transport system to produce energy,
also Glycogen synthesis pathway.
Still, it’s an Energy Parasite;
i.e. can’t synthesize sufficient ATP and is host-
dependent.
(EB RB)
What makes a bacteria this clever to live inside a cell?
Will this protect it from the immune system?
Those who wanna compete should work harder !!
Chlamydia trachomatis
unique cell wall
genome
LPS
Adhesion
Antigenic variation
sub-clinical
Pathogenicity Islands
Compete host for lipids
cryptic plasmid
Chlamydial Anomaly
Sialic acid of mucous membranes
15 serotypes%75
Type III secretion apparatus
Polymorphic membrane transporter
Virulence Factors
1. Chlamydia has a unique cell wall; outer LPS membrane but NO
peptidoglycan. It contains Cystine-rich proteins functionally
equivalent to peptidoglycan. This inhibits phagolysosome fusion.
2. Chlamydia genome encodes for peptidoglycan biosynthesis
enzymes but PGs aren’t synthesized; Hence, resistance to beta-
lactam drugs. Chlamydial anomaly.
3. LPS that causes septic shock.
4. Adhesion to sialic acid receptors on mucous membranes; presence
at sites inaccessible to phagocytes, T-cells & B-cells.
5. Antigenic variation resulting in15 known serotypes.
6. 75% of the infections are sub-clinical still infectious though.
7. Pathogenicity Islands coding for needle-like projection type III
secretion apparatus that inject proteins directly from the bacteria
into the cell cytoplasm and avoid lysosomes.
8. Chlamydia-infested vacuole divert lipids to itself rather than to
another compartment of the host cell.
9. Proteins and regulatory factors produced by the cryptic plasmid.
Polymorphic outer membrane auto-transporter family of proteins,
the putative large cytotoxin, and stress response proteins.
Scientists: What if the immune system attacks?
Chlamydia trachomatis: I’ll get dormant !!
This raised the concept of :Chlamydial persistence
What we know about Chlamydial persistence
• Long-term association between Chlamydia and
host cell in which it’s viable but culture-negative
state.(are detectable but show no growth)
• In vitro persistence show altered growth
characteristics; enlarged, and pleomorphic RBs
that neither undergo binary fission, nor
differentiate back to EBs, but still continue to
replicate their chromosomes.
• Due to failure of secondary differentiation from
RB to EB due to gene down regulation.
• Induced by penicillin treatment, amino acid
starvation, iron deficiency, IFN-γ exposure,
monocyte infection, phage infection, continuous
culture and altered levels of sex hormones.
• Lasts in vitro until removal of the exogenous
stressor.
Aren’t there any gaps ??
1. Penicillin arrests Bacterial Cytokinesis
2. Tetracycline, Erythromycin block Protein
Synthesis
3. Although there’s no immunogenic surface
proteins; still, LPS can be used, but they are
weak !! (vaccine).
Be Aware !!
Chlamydia trachomatis is present as
asymptomatic state within specific hosts
providing a natural reservoir.
ECOLOGY
References
1.http://en.wikipedia.org/wiki/Chlamydia_(bacterium)
2.http://www.ncbi.nlm.nih.gov/pubmed/10411734
3.http://microbewiki.kenyon.edu/index.php/Chlamydia_trachomatis
4. http://www.biomedcentral.com/1471-2180/11/150
5.http://www.sunysccc.edu/academic/mst/microbes/32ctrac.htm
6.http://www.plosone.org/article/info%3Adoi
%2F10.1371%2Fjournal.pone.0007723
7.http://web.uconn.edu/mcbstaff/graf/Student%20presentations/Chlamydia/
Chlamydia%20trachomatis.html
8.http://www.tjclarkdirect.com/bacterial_diseases/chlamydia_trachomatis.htm
9. http://www.austincc.edu/microbio/2421a/ct.htm
10. http://www.ncbi.nlm.nih.gov/pubmed/20470049
11. http://jid.oxfordjournals.org/content/201/Supplement_2/S126.full
12. http://www.hindawi.com/journals/idog/2011/525182/fig2/