Chlamydia trachomatis

transcript

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

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

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/

Chlamydia trachomatis

Education