1. The Role of Cell Organelles in Chlamydia’s Life Cycle
Goals
Study Chlamydia as a vehicle to understand the interrelationships and functioning of various cell organelles.
Identify potential future strategies for treating Chlamydia infections

2. Chlamydia Resources Optional Reading
“Can Chlamydia Be Stopped?” In the May 2005 edition of Scientific American
Good overview of Chlamydia :

3. Chlamydia—a bacterial infection
Chlamydia trachomatis
Common sexually transmitted disease (STD)
~3.5 million Americans are infected with Chlamydia yearly
World's leading cause of preventable blindness
Flies transmit the bacterium to the eye
Causes painful eye condition known as conjunctivitis
Conjunctivitis may lead to Trachoma and then blindness
~600 million infected world-wide with one or more Chlamydia strains

4. Chlamydia (Chlamydia trachomatis)
Signs & Symptoms
85-90% do not show symptoms
Leads to irreversible damage before detected
Testicular or abdominal pain
Painful urination in men
Burning and/or or itching of genitals
Discharge from genitals
Fever (late in disease)

5. Chlamydia (Chlamydia trachomatis)
Possible Complications
Pelvic inflammatory disease 
Infertility (10K women/yr in USA!)
Ectopic or tubal pregnancy
Death of fetus
Eye infections
Blindness
Liver problems
Heart problems
Infant pneumonia
What “normally” happens when bacteria enter a cell?

6. Chlamydia (Chlamydia trachomatis)
Pelvic Inflammatory Disease
Chlamydia over stimulates the body’s immune system
Leads to inflammation of the fallopian tubes
Blocks passage of eggs to uterus
Possible Ectopic and tubal pregnancy
Back to previous slide
Source:

7. Macrophages: “Big Eaters”
Eat dead, injured, and foreign cells
Engulfed cells transported to lysosome for digestion
ID each of the following
1 =
2 =
3 =
4 =
5 =
Phagocytosis—a macrophage snacking on bacteria

8. The formation and functions of lysosomes (Layer 1)

9. The formation and functions of lysosomes (Layer 2)

10. The formation and functions of lysosomes (Layer 3)
What happens when Chlamydia enters a cell?

11. Life Cycle of Chlamydia trachomatis
Most Chlamydia infect columnar epithelial cells
Why not all cells?
Some may infect macrophages—the very cell that is supposed to kill bacteria!
Source:

12. Click here for detailed diagram of membrane structure
Chlamydia Attachment
Click here for detailed diagram of membrane structure
Source:

13. The detailed structure of an animal cell’s plasma membrane

14. How does Chlamydia hide itself within its host cell?
May use a tube (type III secretion apparatus) to secrete proteins that block protein receptors on vesicle surface
Adaptive value?
Divert glycolipids from golgi apparatus
Glycolipids used to “remodel” the surface of the vesicle—adaptive value?
Source: “Can Chlamydia Be Stopped?” Scientific American. May 2005

15. Future strategies for treating Chlamydia
New strategies are required since vaccines are ineffective—why don’t they work?
Knowledge of Chlamydia’s life cycle allows for the development of future drugs
How might a new drug work that would…
Interfere with Chlamydia entering its host cell
Allow a lysosome to attach to a phagocytotic vesicle that contains Chlamydia?
Inhibit Chlamydia’s reproduction and growth within infected cells?
Halt Chlamydia’s ability to spread from cell to cell
Source: “Can Chlamydia Be Stopped?” Scientific American. May 2005

16. Life Cycle of Chlamydia pneumoniae
Colds
Bronchitis
!0% of all pneumonias acquired outside of hospitals (300K in US/yr)
Possibly linked to Arteriosclerosis  leads to strokes & heart attacks
Source:

17. Chlamydia’s Life Cycle (cont.)
Most Chlamydia infect columnar epithelial cells
Some may infect macrophages.
Elementary Bodies (EB)
Rigid outer membrane that is extensively cross-linked by disulfide bonds.
Makes resistant to harsh environmental conditions both inside and outside of the cell
Reticular Bodies (RB)
Non-infectious intracellular form of the Chlamydia.
Metabolically active replicating form of the Chlamydia.
Possess a fragile membrane lacking the extensive disulfide bonds characteristic of the EB.
Source:

18. Summary of Chlamydia’s Life Cycle
The EBs bind to receptors on susceptible cells
Enter cell by phagocytosis
EBs reorganize and become RBs while inside vesicle
The chlamydia inhibit the fusion of the vesicle with the lysosomes and thus resist intracellular killing.
RBs replicate by binary fission and reorganize into EBs.
Each vesicle may contain progeny
Eventually the RB and EB within the vesicle leave the cell by exocytosis
Source:

19. Eukaryotic Cell Structure
1. Nucleus:
Site of DNA, the genetic material
Controls cellular activities
2. Smooth Endoplasmic Reticulum:
Makes lipids and lipids used in plasma membranes
3. Ribosomes:
Site of protein synthesis

20. Eukaryotic Cell Structure
4. Rough Endoplasmic Reticulum:
Membrane bound channel studded with Ribosomes
Makes proteins found in other organelles and proteins exported from the cell
5. Golgi Apparatus:
Modifies newly made proteins, lipids, and carbohydrates
6. Vesicles:
Membrane-bound “balloons” that transport or store substances in cells

21. Eukaryotic Cell Structure
7. Lysosomes:
Sacs containing enzymes that digests worn out cell parts
Digests food ingested by phagocytosis
8. Cytoskeleton:
Protein fibers that help a cell maintain its shape
Some fibers involved with transport of vesicles
9. Mitochondria:
Harvests energy from organic molecules (e.g. sugars and fats) to produce ATP—the energy “currency” of all cells!

22. Trace the pathway of a digestive enzyme from the protein’s gene to the lysosome

23. Pathway of a digestive enzyme from the protein’s gene to the lysosome

24. Pathway of a digestive enzyme from the protein’s gene to the lysosome
1. Gene read to make mRNA 
2. mRNA goes to Rough E.R 
3. Ribosomes read RNA  Inactive protein produced 
4. Protein packaged into vesicles 
5. Vesicles transported to Golgi 
6. Protein modified in Golgi 
7. Protein packaged into vesicles 
8. Vesicles fuse with lysosomes

25. Ribosome on Rough ER Producing a Protein such as GCase
A ribosome reads mRNA to produce a protein molecule
ID of structures...
___________________

26. Rough E.R. to Golgi Apparatus

27. Transport from Golgi Apparatus
Proteins modified by Golgi Apparatus are either...
Used inside cell
e.g._____________________ Or
Exported from cell
e.g. _____________________

28. Membrane Bound Glycolipids
Glycolipids are normally found on membrane surfaces.
Involved with cell – cell recognition

29. Synthesis of Glycolipids in Cells
Which organelle synthesizes lipids?
Where are sugars added to newly made biochemicals?
i.e. where do chemical modifications occur?
(note: sugars are synthesized in the cytoplasm)
Trace the biosynthetic pathway of a glycolipid through the cell from where the lipid is produced to the glycolipids home in the plasma membrane

30. Glycolipid Synthesis and Transport

31. Glycolipid Synthesis and Transport

32. Nucleic Acids: DNA and RNA
are long chains of nucleotides
the “genetic molecules”
Nucleotides
the building blocks (monomers) of DNA and RNA
As monomers they power almost all processes in all cells
e.g. ATP

33. DNA Nucleotides Four Kinds of nucleotides in DNA
A = Adenine T = Thymine
G = Guanine C = Cytosine
Central dogma of Biology
The order of nucleotides in a gene determines the order of ________________________________ in a protein
The order of _____________________ in a protein determines _______________________ of a protein which in turn determines the _____________________ of the protein.

34. Nucleotide Structure Nucleotides are....
the building blocks (monomers) of DNA and RNA
As monomers they transfer energy to power almost all processes in all cells
e.g. ATP

35. ~26,000 genes code for proteins that perform all life functions