The Role of Cell Organelles in Chlamydia’s Life CycleChlamydia ResourcesChlamydia—a bacterial infectionChlamydia (Chlamydia trachomatis)Slide 5Chlamydia (Chlamydia trachomatis)Macrophages: “Big Eaters”The formation and functions of lysosomes (Layer 1)The formation and functions of lysosomes (Layer 2)The formation and functions of lysosomes (Layer 3)Life Cycle of Chlamydia trachomatisChlamydia AttachmentThe detailed structure of an animal cell’s plasma membraneHow does Chlamydia hide itself within its host cell?Future strategies for treating ChlamydiaLife Cycle of Chlamydia pneumoniaeChlamydia’s Life Cycle (cont.)Summary of Chlamydia’s Life CycleEukaryotic Cell StructureSlide 20Slide 21Trace the pathway of a digestive enzyme from the protein’s gene to the lysosomePathway of a digestive enzyme from the protein’s gene to the lysosomePathway of a digestive enzyme from the protein’s gene to the lysosomeRibosome on Rough ER Producing a Protein such as GCaseRough E.R. to Golgi ApparatusTransport from Golgi ApparatusMembrane Bound GlycolipidsSynthesis of Glycolipids in CellsGlycolipid Synthesis and TransportSlide 31Nucleic Acids: DNA and RNADNA NucleotidesNucleotide StructureSlide 35Slide 36Slide 37Slide 38The Role of Cell Organelles in Chlamydia’s Life CycleGoals•Study Chlamydia as a vehicle to understand the interrelationships and functioning of various cell organelles. •Identify potential future strategies for treating Chlamydia infectionsChlamydia ResourcesOptional 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.htmhttp://www.niaid.nih.gov/factsheets/stdclam.htmhttp://pathmicro.med.sc.edu/mayer/chlamyd.htmChlamydia—a bacterial infectionChlamydia trachomatis1. Common sexually transmitted disease (STD) –~3.5 million Americans are infected with Chlamydia yearly2. 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 blindness3. ~600 million infected world-wide with one or more Chlamydia strainsChlamydia (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 fetus2. 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 slideChlamydia (Chlamydia trachomatis) Source: http://adam.about.com/reports/000046.htmMacrophages: “Big Eaters”–Eat dead, injured, and foreign cells–Engulfed cells transported to lysosome for digestionID each of the following1 = 2 =3 =4 =5 =Phagocytosis—a macrophage snacking on bacteriaThe 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 trachomatisSource: 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 AttachmentSource: http://www.chlamydiae.com/images/gifs6dec00/ctattach2.gifClick here for detailed diagram of membrane structureThe detailed structure of an animal cell’s plasma membraneHow does Chlamydia hide itself within its host cell?Source: “Can Chlamydia Be Stopped?” Scientific American. May 2005Chlamydia…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 ChlamydiaSource: “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 cell2. 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 cellLife 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 attacksSource: http://www.chlamydiae.com/docs/biology/biol_devcycle.aspChlamydia’s Life Cycle (cont.)Source: http://pathmicro.med.sc.edu/mayer/chlamyd.htm1. 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 cell4. 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 CycleSource: http://pathmicro.med.sc.edu/mayer/chlamyd.htm1. The EBs bind to receptors on susceptible cells 2. Enter cell by phagocytosis3. EBs reorganize and become RBs while inside vesicle4. 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 exocytosis1. Nucleus:»Site of DNA, the genetic material»Controls cellular activities 2. Smooth Endoplasmic Reticulum:»Makes lipids and lipids used in plasma membranes3. Ribosomes: »Site of