Download The role of biomolecules in Gaucher Disease

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 trachomatis
1. 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)
Chlamydia
(Chlamydia trachomatis)
Possible Complications
1. Pelvic inflammatory disease 
• Infertility (10K women/yr in USA!)
• Ectopic or tubal pregnancy
• Death of fetus
2.
3.
4.
5.
6.
Eye infections
Blindness
Liver problems
Heart problems
Infant pneumonia
8. What
“normally”
happens when
bacteria enter
a cell?
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: 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
The formation and functions of lysosomes (Layer 1)
The formation and functions of lysosomes (Layer 2)
The formation and functions of lysosomes (Layer 3)
What happens when Chlamydia enters a cell?
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: http://pathmicro.med.sc.edu/mayer/chlamyd.htm
Chlamydia Attachment
Click here for detailed diagram of membrane structure
Source: http://www.chlamydiae.com/images/gifs6dec00/ctattach2.gif
The detailed structure of an animal cell’s plasma membrane
How does Chlamydia hide itself
within its host cell?
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?
Source: “Can Chlamydia Be Stopped?” Scientific American. May 2005
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…
1.
2.
3.
4.
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
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/biol_devcycle.asp
Chlamydia’s Life Cycle
(cont.)
1.
Most Chlamydia infect columnar epithelial cells
2.
Some may infect macrophages.
3.
Elementary Bodies (EB)
•
•
4.
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
Summary of Chlamydia’s
Life Cycle
1.
2.
3.
4.
5.
6.
7.
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 100 - 500 progeny
Eventually the RB and EB within the vesicle leave the cell by
exocytosis
Source: http://pathmicro.med.sc.edu/mayer/chlamyd.htm
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
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!
Trace the pathway of a digestive enzyme
from the protein’s gene to the lysosome
Pathway of a digestive enzyme from the
protein’s gene to the lysosome
Pathway of a digestive enzyme from
the protein’s gene to the lysosome
1.
2.
3.
4.
5.
6.
7.
8.
Gene read to make mRNA 
mRNA goes to Rough E.R 
Ribosomes read RNA  Inactive protein produced 
Protein packaged into vesicles 
Vesicles transported to Golgi 
Protein modified in Golgi 
Protein packaged into vesicles 
Vesicles fuse with lysosomes
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. ___________________
–
Rough E.R. to Golgi Apparatus
Transport from Golgi Apparatus
 Proteins modified by
Golgi Apparatus are
either...
Used inside cell
e.g._____________________
Or
Exported from cell
e.g. _____________________
Membrane Bound Glycolipids
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–
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
Glycolipid Synthesis and Transport
Glycolipid Synthesis and Transport
Nucleic Acids: DNA and RNA
Nucleic acids
1.
»
»
are long chains of nucleotides
the “genetic molecules”
Nucleotides
2.
»
»
the building blocks (monomers) of DNA and RNA
As monomers they power almost all processes in
all cells
–
e.g.
ATP
DNA Nucleotides
1.
2.
Four Kinds of nucleotides in DNA
A = Adenine
T = Thymine
G = Guanine
C = Cytosine
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
~26,000 genes
code for
proteins that
perform all
life functions