The Role of Cell Organelles in Chlamydia

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The Role of Cell Organelles in Chlamydias 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

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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

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Chlamydiaa 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

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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)

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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

1. What normally happens when bacteria enter a
   cell?

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Chlamydia (Chlamydia trachomatis)

• Pelvic Inflammatory Disease
• Chlamydia over stimulates the bodys 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 http//adam.about.com/reports/000046.htm
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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

Phagocytosisa macrophage snacking on bacteria
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The formation and functions of lysosomes (Layer 1)
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The formation and functions of lysosomes (Layer 2)
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The formation and functions of lysosomes (Layer 3)
What happens when Chlamydia enters a cell?
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Life Cycle of Chlamydia trachomatis

• Most Chlamydia infect columnar epithelial cells
• Why not all cells?
• Some may infect macrophagesthe very cell that is
  supposed to kill bacteria!

Source http//pathmicro.med.sc.edu/mayer/chlamyd.
htm
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Chlamydia Attachment
Click here for detailed diagram of membrane
structure
Source http//www.chlamydiae.com/images/gifs6dec0
0/ctattach2.gif
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The detailed structure of an animal cells plasma
membrane
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How does Chlamydia hide itself within its host
cell?

• Chlamydia
• 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
  vesicleadaptive value?

Source Can Chlamydia Be Stopped? Scientific
American. May 2005
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Future strategies for treating Chlamydia

• New strategies are required since vaccines are
  ineffectivewhy dont they work?
• Knowledge of Chlamydias 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 Chlamydias reproduction and growth
  within infected cells?
• Halt Chlamydias ability to spread from cell to
  cell

Source Can Chlamydia Be Stopped? Scientific
American. May 2005
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Life Cycle of Chlamydia pneumoniae

• 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 http//www.chlamydiae.com/docs/biology/bio
l_devcycle.asp
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Chlamydias 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 http//pathmicro.med.sc.edu/mayer/chlamyd.
htm
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Summary of ChlamydiasLife Cycle

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

Source http//pathmicro.med.sc.edu/mayer/chlamyd.
htm
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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

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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

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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 ATPthe energy
  currency of all cells!

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Trace the pathway of a digestive enzyme from the
proteins gene to the lysosome
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Pathway of a digestive enzyme from the proteins
gene to the lysosome
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Pathway of a digestive enzyme from the proteins
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

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Ribosome on Rough ER Producing a Protein such as
GCase

• A ribosome reads mRNA to produce a protein
  molecule
• ID of structures...
• ___________________
• ___________________
• ___________________
• ___________________

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Rough E.R. to Golgi Apparatus
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Transport from Golgi Apparatus

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

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Membrane Bound Glycolipids

• Glycolipids are normally found on membrane
  surfaces.
• Involved with cell cell recognition

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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

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Glycolipid Synthesis and Transport
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Glycolipid Synthesis and Transport
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Nucleic Acids DNA and RNA

• Nucleic acids
• 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

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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.

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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

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• 26,000 genes code for proteins that perform all
  life functions

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