Flashcards
Lecture 7
Flashcards do conjunto (52)
- 1Bacterial Toxins- first VF to be identified and studied
- relatively easy to isolate and purify
- biochemical experimentation
- often very specific for target molecules
- provide effective vaccines - 2Toxins are produced by a wide range of bacteria for a wide ride of purposes, usually involving ______________.killing or impairing other cells or organisms
- 3In many cases toxins have a clear benefit 1. 2. 3. Caveat1. Disrupt cytokine signaling
2. Kill professional phagocytes
3. Kill cells to release iron and nutrients
-> it's not obvious is ALL cases how the toxin provides a benefit for the bacteri - 4Botulinum Toxin - Abbreviation - Produced by ? - Problems come from?-BoNT or BOTOX
- Clostridium botulinum
- Problems come from eating the toxin produced in anaerobic food or clostridial spores
- Bacteria do not colonize the intestinal tract well
- Not well designed to be a pathogen - 5Botulinum Toxin - In nature - Purpose?- C. botulinum normally lives in anaerobic non-circulating water (not a lot of nutrients)
- Toxins kill visitors that then fall into the water to become food
- Toxin can travel up the food chain - 6Figuring out the "Why's" of Toxins isn't simple because....- sometimes you have to examine the environment niches the bacteria occupy
- many toxins are associated with PAIs or other HGT elements
-> not normal parts of the bacterial genome, lysogenic phages carry toxins - 7Characteristics of Bacterial Toxins Definition of Toxin- Come in all shapes and sizes with even more different naming methods
TOXIN: any type of VF, secreted or not, that is toxic to the human or animal host - 8Naming can be based on...- tissue type they attack
- just a simple letter
- named in order of discovery
- species or disease they are from
- enzymatic activity
- biochemical property
- immune reactivity - 9NAMING - Tissue Type Examples- cytotoxin: wide variety of cells
- neurotoxin: nerve cells
- hepatotoxin: liver cells
- leukotoxin: leukocytes
- cardiotoxin: heart cells
- enterotoxin: intestinal cells
- verotoxin: vero cells - 10NAMING - Simple Letter Name ExampleExotoxin A
- Pseudomonas aeruginosa - 11NAMING - Discovery Orderalpha-epsilon toxins
Clostridium perfringens - 12NAMING - Species or Disease Examples-Cholera Toxin (CT), Cholera from Vibrio Cholerae
-Shiga Toxin (ST), from Shigella
- Diphtheria Toxin (DT), diphtheria, from C. diphtheriae
- Tetanus Toxin (TeNT), tetanus, from C. tetani
- Botulinum Toxin (BoNT), botulism, from C. botulinum - 13NAMING - Enzymatic Activity ExamplesAdenylate cyclase
- Bordetella pertussis, Whooping Cough
Lecithinase
- C. perfringens, Gangrene - 14NAMING - Biochemical Property ExamplesHeat-labile Toxin (HLT)
Heat-stabile Toxin (HST)
-> both found in certain strains of E.coli - 15NAMING - Immune Reactivity ExamplesBoNT's have seven serotypes (A-G)
- Abs to one won't react to the other
BoNT/A, BoNT/B, BoNT/C, etc. - 16Toxins can have more than one name (Examples)- Shiga-like Toxin (SLT), Verotoxin
-> same toxin from E.coli
- alpha-toxin, Lecithinase
-> same toxin from C. perfringens
- Osteolytic toxin, Dermonecrotic toxin, Mitogenic Toxin, PMT
-> same toxin from Pasturella multocida - 17Why is a single name usually not enough to be specific?There are many different types of the same toxin (e.g. Verotoxins, alpha toxins)
- To avoid confusion, the bacteria name is used - 18Classifying Toxins- Exotoxin
- Endotoxin
- Exoenzymes/Effector Protein - 19Exotoxina toxin that is excreted from the bacteria into the media
- usually protein
- "standard" - 20Endotoxina toxin that is part of the bacterial surface and is released during cell lysis
- usually lipid-like molecules
- not secreted - 21Exoenzymes/Effector Proteinstoxins that are injected directly into the host cell via secretion systems
- 22Classifying toxins by mechanism of action: Type I-IIIType I: binds to the target cell surface and works extracellularly (Superantigens)
Type II: Act on eukaryotic cell membranes to destroy their integrity (phospholipases, pore-forming cytotoxins)
Type III: activates or inactivated an intracellular target or signaling pathway (A-B type toxins) - 23Different kinds of bacterial toxins- Nonprotein toxins
-> endotoxins, mycolactones
- Protein exotoxins (secreted)
-> Type I-III
- Exoenzymes/Effectors - 24Endotoxins- integral bacterial membrane components
-> LPS, LTA, phosphatidylglycerol
- LPS toxicity is mediated by Lipid A
- Septic Shock
-> over activation of immune cells - 25CAUTION when treating Endotoxins because...- for some Gram-, caution when treating systemic bacterial infections that contain endotoxins with antibiotics that destroy the cell wall, because all you're doing is released the endotoxin into the "environment"
- 26Jarisch-Herxheimer Reaction and Endotoxins- Treating syphillis with penicillin or tetracycline
- lesions due to the bodies own inflammatory response
-> 50% primary, 90% secondary syphillis - 27Some pathogens purposefully release parts of their cell membrane to cause...toxic effects
e.g. Bordetella pertussis, Whooping Cough - 28Pertussis - Endotoxin Disease- Bordetella tracheal cytotoxin (TCT)
- Arrests ciliary movement
- Extrudes ciliated cells from the epithelium
- Releases inflammatory cytokine IL-2
- Coughing the only way to expel mucus, predisposes individual to 2ndary infections - 29Nonprotein Toxins - Mycolactones- polyketide-derived, lipid-like molecules produced to enhance growth
- Cytotoxic and immunosuppressive prevents inflammation and pain, promotes skin lesion growth - 30Protein Toxin - Type I + exampleSuperantigens
- over activate immune system
- TSS: Toxic Shock Syndrome Toxin (TSST), Staph aureus was found to be colonizing the vagina and growing in a particular type of tampon
- (TSLS): Strep pyogenes toxin production in preexisting skin infections - 31Protein Toxin - Type IIMembrane-Disrupting Toxin
- Pore-forming toxins: create channels or holes
- Destabilizing toxins: destroy integrity of membranes - 32Protein Toxin - Type II Example- alpha toxin of C. perfringens destroys lecithin in animal cell membrane and contributes to gangrene by destroying cells and tissue
- 33Protein Toxins - Type IIIA-B Toxins
- A: toxic/enzymatic, active
- B: part binds to the host cell moves A domain into the cell
Binding: Translocation - movement of the A portion from the outside of cell to inside - 34Protein Toxins - Type III Simple A-B toxins-Single polypeptide chain
- Usually separated by proteolytic cleavage
- e.g. Diphtheria
- B domain binds to host receptor, endocytosis, translocation, release of A domain - 35Protein Toxins - Type III Complex A-B ToxinsLarge multi-subunit complexes
- A portion attached to multi-subunit B-portion
- e.g. Cholera, Anthrax, Pertussis - 36A domain mechanism of Toxicity- Many A parts of A-B toxins have the same enzymatic activity
- ADP-ribosyltransferases: move ADP-ribosyl groups from NAD to host protein - 37A-B Toxin ADP-Ribosyltransferases- The host protein affected, and therefore the results of the added group, depends on the toxin
- 38Not all A sub-units are ADP-Ribosyltransferases. Explain.- Shiga Toxin A subunit cleaves rRNA, Also shuts down protein synthesis
- Botulinum Toxin A subunits are zinc-dependent metalloproteases that cleave neuron-specific proteins
Cause paralysis
- Anthrax has two A subunits
Adenyl cyclase
Zn-dependent protease - 39Exoenzymes/Effectors- Proteins directly injected into the host cell
- Toxic activities are similar to A-B domains, no need for B domains
- Harmless unless they can be injected into the host cell - 40Corynebacterium diphtheriae- Gram+ rod
- non-spore forming
- nonmotile
- aerobic
- pleiomorphic - 41Diphtheria- Corynebacterium diphtheriae
- Commonly vaccinated for where money and health-care is available
- Normally a disease in children and can be fatal in untreated individuals - 42Diphtheria Toxin (DT)- one of most well studied
- first example where the entire disease could be explained by the action of one molecule
- helped promote concept of virulence factors - 43Diphtheria Pathogenesis - Colonization - Adherence - Invasion- Colonization: inhalation of aerosols, bacteria colonize the throat
- Adherence: remain in place, mucosal epithelia
- Invasion: begin secreting DT killing mucosal cells, lymph node swelling, formation of pseudomembrane - 44Pseudomembrane- greyish layer that extends into the throat and sometimes into the lungs
- composed of fibrin, bacteria, immune cells - 45Diphtheria Disease Symptoms- Pseudomembrane adheres tightly to the underlying tissue, removing causes bleeding
- sudden death can occur from suffocation - 46Diphtheria Toxicity- DT is slowly released into the bloodstream
- causes organ damage and eventual organ failure
- Serious forms of the disease: heart damage, lung damage, skin lesions - 47DT Production- DT is encoded on a group of bacteriophages (beta and w corynebacteriophages)
- production enhanced in low iron conditions - 48DT Production- DtxRDtxR: diphtheria toxin regulation - repressor protein that binds iron
- HIGH: binds to iron, binds to the DT operator, prevents tx of the toxin
- LOW: no iron to bind, no binding to operator, toxin tx ensues - 49DT Production, why?- to increase iron supply?
- increase spread from person to person?
- phage using bacteria to spread? - 50Mechanism of Diphtheria Toxin- Simple Type III A-B Toxin
- B fragment made of 2 domains:
R - binds to HB-EGF receptor
T - translocation domain, inserts into the membrane at low pH - 51Specifics of Diphtheria Toxin- R domain binds to HB-EGF
- DT is endocytosed
- Low pH causes protonation of acidic a.a.'s making them less hydrophilic
- Changes the conformation of DT
- T domain inserts into vesicle, creates a pore that translocates the A, bind reduced, releases A into cytoplasm - 52—
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- College Pathogenic Microbiology FlashCards sobre Lecture 7, criado por Bella Paniagua em 27-10-2015.
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- Bella Paniagua
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