Microbiology Lecture 8 - Pathogenesis and Toxigenicity Part 1
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What are toxins ?
What are they composed of ?
Can toxins be fatal ?
Toxin: microbial poison; any substance that is toxic to a cell
Toxins are proteins made by living organisms (and other organisms) that have a negative or toxic effect on the host
Sometimes the effect of toxins can be fatal to the host
What is Toxigenicity ?
Can an organism be described as "Toxogenic" ?
Can the DNA for Toxins be transferred on a plasmid?
The capacity of microbes to make and secrete toxins.
Microbes can be described as toxigenic.The organism carries genes for these toxic molecules on their chromosome
Some toxins are plasmid-borne and can be shared between related species by horizontal/lateral transfer
What is Toxinosis ?
What is Intoxication ?
What is Toxemia ?
Toxinosis : disease caused by a toxin.Requires the pathogen to colonize, grow and produce toxins that are secreted.
Intoxication: disease that results from ingestion of the (pre-formed) toxin does not require the pathogen
Toxemia: the presence of toxins in the blood
What is Toxicology ?
What is a Toxoid ?
What are Antitoxins ?
Toxicology: the study of toxins, including structure, mechanism of action, regulation, etc.
Toxoid: attenuated (weakened) toxin; used to as vaccines to stimulate a protective immune response
Antitoxins: antibodies produced by the body (animal host) to neutralize toxins
Can a Toxin cause cytolysis ?
Do Toxins interfere with the metabolic process?
What are these effects of Toxins ?
- emetic - vomiting
- Neoplastic - tumor growth
What are proenzymes ?
Are produced as proenzymes within the microbe; this form is inactivy.The toxin is then activated once it leaves the cell via Enzymatic cleavage or phosphorylation
How are bacterial toxins listed ?
What are toxins called that are harmful to other bacteria ?
What are Bacteriocins called that are beneficial to humans ?
What does the term antigenic mean ?
Bacterial toxins harmful to humans are listed by the body system they target.
If toxic to other bacteria, they are called bacteriocins.If these toxins are used in the treatment of human bacterial infections, they are called antibiotics
Toxins are antigenic; stimulates the immune system
What are toxins made by fungi called ?
What is algal toxin called ?
- Cyanobacteria: Bacteria
- Dinoflagellates: Protozoa
Are the cause of shellfish poisoning in humans
What are endotoxins and exotoxins ?
Exotoxins: toxins secreted by live bacteria
Endotoxins: released when the bacteria dies
Based on Definition 1: Based on the viability of the bacterial cell What are the function of endotoxins and exotoxins ?
Exotoxins: toxins secreted by live bacteria
Endotoxins: released when the bacteria dies
Based on Definition 2: Based on the location of the toxins in relation to the bacterial cell , what are the function of endotoxins and exotoxins ?
Exotoxins: toxins released into the surrounding area
Endotoxins: are critically associated with the bacteria
Based upon Definition 3: Based on the action of the toxin , what are the funtion of endotoxins and exotoxins ?
Exotoxins: work on intracellular targets of the host cell
Endotoxins: work at the surface of the host cell
Are exotoxins made by both gram - and gram + bacteria ?
Do all bacteria make exotoxins ?
Where are exotoxins made?
Are they enzymes ?
In the cytoplasm - ribosomes
Whic toxins are more potent , intracellular or extracellular ?
How do conformations effect the way toxins leave and enter the cell ?
Does conformation effect the function of the toxin ?
Some toxins are exported across the plasma membrane into the host cell and then folded to the correct conformation.Active once the correct conformation is achieved.
Some toxins are made and folded within the bacterial cell and are only exported if they have the correct conformation.
Where do the following toxins act ?
Neurotoxins: act on the nervous system
Enterotoxins: act on the gastrointestinal tract (also known as the enteric system).Commonly associated with food poisoning
- Nephrotoxins: damage the
Hepatotoxins: damage the liver
What are some effect of neurotoxins ?
Can result in flaccid (limp) or rigid paralysis .E.g. botulinum toxin made by Clostridium botulinum; etiological agent for botulism, a severe form of food poisoning
Can cause rigid paralysisE.g. tetanus toxin made by Clostridium tetani; etiological agent for tetanus (or lockjaw)
What are some effects of enterotoxins ?
Are exotoxins that specifically target the intestinal mucosa
- Affect cAMP levels
- Result in increase elimination of water from intestinal cells
Cause vomiting and diarrhea
What are cytotoxins ?
because the action of the toxin is within the cytoplasm
The toxin is secreted directly into the cytosol in a contact-dependent manner
Advantages -Efficient: poison enters only the target cell
Selective: intracellular target is specific
Do gram - or gram + cytoxins make a pore or inject it ?
gram + make a pore
gram - inject it
What is Type III and Type IV toxin injection of gram negatve bacteria ?
Molecular syringes that resemble flagella (Type III)
Molecular syringes that resemble conjugative pili (Type IV)
What are AB toxins ?
What are the differences between the unit ?
A Toxin enters without the aid of the bacteria
B domain/subunit Binds to cell surface receptors of host Helps to translocate the A domain/subunit A domain/subunit.
Is transferred across the plasma membrane into the host cellEnters the cytoplasm and enzymatically acts on host targets
What is Diptheria Toxin ?
-Diphtheria toxin isAn AB toxin Produced by Corynebacterium diphtheriae
-The A sub-unit inhibits protein synthesis by blocking the transfer of an amino acid from the tRNA to the polypeptide.Specifically inactivates elongation factor 2 (EF-2)
-Diphtheria is a childhood disease of the respiratory system
What is Botulin ?
Botulin (also called Botulinum toxin)
Produced by Clostridium botulinum.Is a group of seven related A-B toxins; 1A + 1B
Are the most potent biological toxins known
Binds to the pre-synaptic membranes of stimulatory motor neurons found at the neuromuscular junction.Blocks the release of acetylcholine (neurotransmitter).This prevents the muscle from receiving an excitatory signal.No muscle contraction
What is Tetanospasmin (also called tetanus toxin ) ?
- Produced by Clostridium tetani
- An A-B toxin Targets the motor neuronsIs transported to the spinal column and binds to ganglioside lipids of inhibitory neurons
Inhibitory neurons produce glycine which stops the release of acetylcholine, which causes muscles to contract
Tetanospasmin blocks the release of glycine, resulting in continuous contraction of muscles.
What is Cholera Toxin (also called choleragen) ?
Cholera toxin is called choleragen
Produced by Vibrio cholerae Is an A-B toxin: 1A + 5B Binds to the ganglioside GM1 of intestinal epithelial cells
Activates the enzyme, adenyl cyclase which causes increased production of cAMP
cAMP prevents the movement of Na+ in cells and the net movement of Cl- out of cells
The change in ion concentration results in the secretion of large amounts of water from the small intestine
Water reabsorption by the large intestine is slower than water loss
Patients suffer severe dehydration
How do Cytolytic Toxins work ?
Work by enzymatically attacking the cell causing cell lysis.The action of these toxins are most easily observed with erythrocytes, hence they are often called hemolysins
They also work on cells other than erythrocytesAction is observed by streaking the organism on (sheep’s) blood agar plates
Are these all types of Cytolytic Toxins?
C. Lecithinases or phospholipases
What are Hemolysins ?
Hemolysins they are Produced by: staphylococci, streptococci, clostridia, Escherichia
Hemolysis: Lyses red blood cells (erythrocytes)
- Results in anemia
- Purpose:Allows pathogen greater access to iron
Action: Enzyme causes pore-formation in the plasma membrane,Death is by necrosis (lysis of the cell where the cellular contents spill out and damage neighboring cells)Also destroys leucocytes (white blood cells
What are the three types of hemolysis ?
Alpha hemolysis: the partial destruction of erythrocytes (RBCs)
Beta hemolysis: the complete destruction of erythrocytes (RBCs)
Gamma hemolysis: no hemolysis
What to streptococci Hemolysins work on ?
Hemolysins produced by the streptococci Does not work on the phospholipids of the cell membrane. Instead, works on sterols.Similar effect to hemolysins in staphylococci.
Example: streptolysin A; streptolysin O
What do Lecithinases/Phospholipases do ?
Lecithin is a phospholipid that protects cells from oxidative stress
- Action: Enzymes that hydrolyze membrane phospholipids (e.g. lecithin)
- Purpose: disrupt plasma membrane Damages the cell resulting in cell death and release of cellular contents
e.g. alpha toxin of Clostridium perfringens
What are leukocidins ?
Produced by: staphylococci, streptococci, and some bacilli
Result:Destroy host white blood cells (leukocytes)causes the disintegration of macrophages and neutrophils
Purpose:Prevents phagocytosisReduces the immune response
How do Leukocidins function ?
Action:Enzyme attaches to the plasma membrane of leukocytes
Causes pores to form Results in the degranulation of lysosomes within leukocytestriggers the release of lysosomal enzymes into the cytoplasm
What is Leukostatin ?
Leukostatin Produced by several species of bacteria
Action: Interferes with the ability of phagocytes to phagocytize cellsPurpose: anti-phagocytic
What is Collagenase ?
Collagenase Produced by: clostridia
- Action: hydrolyzes collagen Collagen: the fibrous protein constituent of bone, cartilage, tendon, and other connective tissue.
- Forms the framework for connective tissuesPurpose: Allows for deeper penetration into tissue
What is Hyaluronidase ?
Produced by: staphylococci, streptococci, clostridia•
Also called spreading factor•Action: Hydrolyzes hyaluronic acid (HA)•HA is a glue-like substance (mucopolysaccharide) that helps to hold cells of tissues together; sometimes referred to as “tissue cement”.•
Purpose: tissue penetration•Allows bacteria to pass between epithelial cells and move deeper into tissues
What is Elastase ?
ElastaseProduced by several bacterial species (next slide)
Action: Breaks down elastin and lamininElastin is an elastic protein found in connective tissue, along with collagen.
It allows many tissues in the body to resume their shape after stretching or contracting.Laminin is a major protein of the basal lamina, part of the basement membrane of tissues and organs
Purpose: Allows for deeper penetration into tissue.
What are proteases ?
Proteases Proteases are also referred to as peptidases or proteinases
Purpose: to destroy or cleave proteins
Several types of microbial proteases are important in establishing an infection
What is the purpose of immunoglobulin Protease ?
Immunoglobulin a Protease Produced by: Streptococcus pneumoniae IgA plays an important role in protecting the host against respiratory pathogens
Action:Cleaves IgA into the two parts—the Fab portion and the Fc portionPurposeInactivates IgA; decreases the immune response
What is the purpose of Cysteine protease ?
Cysteine proteaseProduced by Streptococcus pyogenes
- Action:Degrades proteins
- Purpose: destroys antibodies decreases the immune response, especially opsonization and antigen presentation (specific immunity)
Inactivates complement (innate immunity)
What is Coagulase ?
Coagulase•Produced by: Staphylococcus aureus and Yersenia pestis•Boils and abscesses are associated pathologies.•Action: Catalyzes blood clotting;•coagulates fibrinogen present in plasma;•accelerates coagulation rates during an infection•Fibrinogen is a glycoprotein produced by the liver and present in blood plasma; is essential for blood clotting.•Purpose:•Facilitates resistance to phagocytosis•Protects the pathogen from phagocytic leukocytes such as macrophages and neutrophils
What are Kinases ?
KinasesAlso called fibrolysinsProduced by:staphylococci (staphylokinase)streptococci (streptokinase)Action: digests blood clots; breaks down fibrinPurpose: Prevents isolation of infectionWhen coagulation occurs, pathogens are trapped in a local area in the blood stream and cannot disseminateDissolving blood clots allows for greater tissue penetration and the spread to other areas of the body
What are Lipases ?
Lipases Present in staphylococciAction: digests lipids
Purpose: Helps bacteria to colonize oily skin
What is nuclease ?
NucleaseRefers to deoxyribonuclease(Dnase)Produced by: staphylococci, streptococciAction: cleaves DNAPurpose:Destroys leukocytes; anti-phagocyticLowers the viscosity of exudate, giving the pathogen greater latitude for spreadingExudate: fluid that has escaped out of tissues or blood vessels due to injury or inflammation
What are Beta-Lactamases ?
Beta-lactamasesPresent in many different species, especially staphylococci and streptococciAction: cleaves members of the penicillin drug familyPurpose: Confers resistance to beta-lactam antibioticsBeta-lactam drugs work on peptidoglycan, preventing cell wall synthesis, ultimately leading to cell deathAllows pathogen/infection to persist
What is Mucinase ?
MucinasePresent in Entamoeba histolytica (protozoa)Enzyme digests the protective coating on mucous membranesIs a virulence factor in amebic dysentery
What is Keratinase ?
KeratinaseDigests keratin, the principal component of skin and hairPresent in dermatophytesDermatophytes: fungal species that reside in the epidermal layer of the skin.Organisms cause superficial cutaneous infectione.g. ring worm (also called tinea)
What are superantigens ?
SuperantigensProteins that activate a large number of T-lymphocytes, without stimulation by specific antigensPresent in bacteria and virusesActivates T-cells with different antigen specificitiesEffect: T-cells release a large amount of cytokines, which may lead to organ failure and immunosuppression
Examples:Staphylococcal enterotoxins (specifically SE-B)There are 24 different typesStaphylococcal toxic shock syndrome toxin, 1 and 2
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