The Role of Cell Organelles in Chlamydia’s Life Cycle Goals Study Chlamydia as a vehicle to...
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Transcript of The Role of Cell Organelles in Chlamydia’s Life Cycle Goals Study Chlamydia as a vehicle to...
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
Chlamydia Resources
Optional Reading
• “Can Chlamydia Be Stopped?” In the May 2005 edition of Scientific American
• Good overview of Chlamydia :http://www.cdc.gov/std/Chlamydia/STDFact-Chlamydia.htm
http://www.niaid.nih.gov/factsheets/stdclam.htm
http://pathmicro.med.sc.edu/mayer/chlamyd.htm
Chlamydia—a bacterial infection
Chlamydia trachomatis1. Common sexually transmitted disease (STD) – ~3.5 million Americans are infected with Chlamydia yearly
2. 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
3. ~600 million infected world-wide with one or more Chlamydia strains
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)
Possible Complications1. Pelvic inflammatory disease
• Infertility (10K women/yr in USA!)• Ectopic or tubal pregnancy • Death of fetus
2. Eye infections3. Blindness4. Liver problems5. Heart problems6. Infant pneumonia
Chlamydia (Chlamydia trachomatis)
8. What “normally” happens when bacteria enter a cell?
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
Chlamydia (Chlamydia trachomatis)
Source: http://adam.about.com/reports/000046.htm
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
Life Cycle of Chlamydia trachomatis
Source: http://pathmicro.med.sc.edu/mayer/chlamyd.htm
• Most Chlamydia infect columnar epithelial cells • Why not all cells
?
• Some may infect macrophages—the very cell that is supposed to kill bacteria!
Chlamydia Attachment
Source: http://www.chlamydiae.com/images/gifs6dec00/ctattach2.gif
Click here for detailed diagram of membrane structure
How does Chlamydia hide itself within its host cell?
Source: “Can Chlamydia Be Stopped?” Scientific American. May 2005
Chlamydia…1. May use a tube (type III secretion
apparatus) to secrete proteins that block protein receptors on vesicle surface
• Adaptive value?
2. Divert glycolipids from golgi apparatus
• Glycolipids used to “remodel” the surface of the vesicle—adaptive value?
Future strategies for treating Chlamydia
Source: “Can Chlamydia Be Stopped?” Scientific American. May 2005
• 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…1. Interfere with Chlamydia entering its host cell
2. Allow a lysosome to attach to a phagocytotic vesicle that contains Chlamydia?
3. Inhibit Chlamydia’s reproduction and growth within infected cells?
4. Halt Chlamydia’s ability to spread from cell to cell
Life Cycle of Chlamydia pneumoniaeChlamydia
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: http://www.chlamydiae.com/docs/biology/biol_devcycle.asp
Chlamydia’s Life Cycle (cont.)
Source: http://pathmicro.med.sc.edu/mayer/chlamyd.htm
1. Most Chlamydia infect columnar epithelial cells
2. Some may infect macrophages. 3. 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
4. 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.
Summary of Chlamydia’sLife Cycle
Source: http://pathmicro.med.sc.edu/mayer/chlamyd.htm
1. The EBs bind to receptors on susceptible cells
2. Enter cell by phagocytosis
3. EBs reorganize and become RBs while inside vesicle
4. The chlamydia inhibit the fusion of the vesicle with the lysosomes and thus resist intracellular killing.
5. RBs replicate by binary fission and reorganize into EBs.
6. Each vesicle may contain 100 - 500 progeny
7. Eventually the RB and EB within the vesicle leave the cell by exocytosis
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
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
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!
Eukaryotic Cell Structure
Ribosome on Rough ER Producing a Protein such as GCase
– A ribosome reads mRNA to produce a protein molecule
ID of structures...1. ___________________2. ___________________3. ___________________4. ___________________
Transport from Golgi Apparatus Proteins modified
by Golgi Apparatus are either...Used inside cell e.g.____________________
_
Or
Exported from celle.g.
_____________________
Membrane Bound Glycolipids
– Glycolipids are normally found on membrane surfaces.
– Involved with cell – cell recognition
Synthesis of Glycolipids in Cells
1. Which organelle synthesizes lipids?2. Where are sugars added to newly made
biochemicals? i.e. where do chemical modifications occur?
(note: sugars are synthesized in the cytoplasm)
3. Trace the biosynthetic pathway of a glycolipid through the cell from where the lipid is produced to the glycolipids home in the plasma membrane
Nucleic Acids: DNA and RNA
1. Nucleic acids» are long chains of nucleotides» the “genetic molecules”
2. Nucleotides» the building blocks (monomers) of DNA and
RNA» As monomers they power almost all
processes in all cells– e.g. ATP
DNA Nucleotides1. Four Kinds of nucleotides in DNA
A = Adenine T = Thymine
G = Guanine C = Cytosine
2. Central dogma of Biology
a. 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.
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