TB Testing Continues for 1,900 Fairfax Co. Students, FacultyOcala burn victim's death coincides with bacterial infections at ShandsAcinetobacter in Healthcare SettingsMMG 301 Exam 3Week 1Lecture 30: Vocab-Virulence factor- A pathogen-produced substance (usually a protein, enzyme, adherence factor, or toxin) that promotes the establishment and maintenance of disease. Adherence proteins- Proteins that bind bacteria to specific host receptors (glycoproteins, polysaccharides). Hyaluronidase- An enzyme virulence factor that breaks down hyaluronic acid in connective tissue in order to invade the host. Collagenase- An enzyme virulence factor that breaks down collagen in connective tissue in order to invade the host.Coagulase- An enzyme virulence factor that works by causing blood to clot; prevents access by host immune cellsStreptokinase- An enzyme virulence factor that destroys fibrin blood clots in order to pass these blood clots and invade tissues.Elastase- An enzyme virulence factor that breaks down host cell membranes in order to invade the host cell.Leukocidins- Bacterial exotoxins (secreted to the surrounding) that are cytotoxic to host cells (degrade host cells resulting in lysis) and act against white blood cells thus decreasing the hosts immunity.Lecithinases- A type of phospholipase that acts upon lecithin. It can be produced by Clostrodium perfringens or listeria monocytogens. This toxin can cause myonecrosis and hemolysis. Hemolysins- A bacterial exotoxin that is cytotoxic to host cells. This toxin was originally discovered because of lysis of red blood cells, but also works on other cell types; distinctive clear zones around colonies on blood agar plate (lysis).Endogenous pyrogens- Released by the host in response to endotoxins (cell-bound lipopolysaccharides that are usually released upon lysis of the bacterial cell). Endogenous pyrogens regulate temperature.Limulus amebocyte assay- An assay for endotoxins: a pharmaceutical solution may be sterile, bit still contain fragments of dead bacteria and endotoxins. A way to assay for endotoxins which maybe in the solution. The limulus amebocyte is sensitive to endotoxins and lysis upon contact with them. Recombinant DNA advances have yielded simpler tests that negate the need for limulus blood.Exotoxins- Bacterially- produced toxins that are usually small proteins that are released into the cell sorroundings (extracellular toxins). Three types; cytolytic toxins, AB toxins, and superantigens(hyperstimulation of immune cells)A-B toxin- Consist of two subunits: B binds to host surface, A crosses into the cellEnterotoxins- Exotoxins that affect the small intestine. “Entero”-- IntestineLD50- Lethal dose that kills 50% of a test population.Nosocomial infections- A hospital-acquired infection.Concepts:- review opportunistic, accidental, obligate pathogens and major points of adherence, invasion, colonization; review each of the given examples of virulence factors involved inadherence, invasion and colonizationo Opportunistic pathogens- take advantage of opportunities. The opportunity can be an injury (invasion process is already done by pathogen) or weak immunityo Accidental pathogen- Bacterial pathogens that cause disease accidently. The disease limits the spread of the bacteria to another host. Ex. tetanus, botulism, gas gangrene (C. perfringens), gastroenteritis (C. difficile)o Obligate pathogens- Bacteria that must cause disease in order to be transmitted from one host to another. They must infect the host in order to survive. Ex. mycobacterium tuberculosis, and Treponema pallidum.o Adherence- Aided by: glycocalyx (adherence and biofilm formation), Adherence proteins (bind bacteria to specific host receptors), fimbriae and pili (bind to specific receptors), lipoteichoic acid (aid in attachment)o Invasion- Entry of the pathogen through the epithelium. Usually occurs through breaks of lesions of the mucosa or skin. Invasion is not required in some diseases since some bacteria produce harmful toxins- cholera (vibrio cholera)o Colonization and growth- Multiplication and growth of microbes after entry into host tissues that have a suitable environment with proper nutrients, pH, trace minerals, and temperatureo Ex. of virulence factors that aid in invasion of the host: Hyaluronidase- breaks down hyaluronic acid in connective tissue Collagenase- breaks down collagen in connective tissue Streptokinase- destroys fibrin of blood clots to get to tissues Coagulase- works by causing blood clots to hide from the immune system Elastase- breaks down host cell membranes- what are bacteremia and septicemiao bacteremia- Occurs when there is enough growth that viable bacteria enter the circulating bloodstream or lymphatic systemo septicemia- bacteremia with sepsis- a severe, life-threatening systemic inflammatory response, often in response to bacterial toxins (sepsis)- what are the three common types of exotoxinso Cytolytic toxins- degrade host cells resulting in lysiso AB toxins- consist to two subunits: B binds to host surface, A crosses into cello Superantigens- hyperstimulate immune cells- tissue inflammation and damage- how can virulence of a particular pathogen be measuredo Virulence can be quantitated using the LD50 test in mice. Can be measured by exposure to various doses of a bacterial path. LD50 is very high for extremely pathogenic microbes- few cells are needed for efficient killing of the mouse host.- review the mode of action of A-B toxins of tetanus, botulism, and cholera; why is there a large fluid loss in cholera; what are spastic paralysis and flaccid paralysiso Diphtheria toxin- extremely cytotoxic (only one required to kill host cell) An AB toxin: two fragments B binds to the host cell receptors; after binding, a protease cleaves between the A and B The A fragment then enters the cell and blocks tRNA from entering the ribosome by enzymatic modification ADP-ribose is attached to elongation factor 2 and protein synthesis is prevented. Called ADP- ribosylation.o Botulism toxin- clostridium botulinum First reported in 1793. 7 types of botulinum toxin known. Are the most toxic substances known Usually the result of improper food preservation Toxin binds to presynaptic membranes of motor neurons (synapsing withmuscle fibers) resulting in paralysis (flaccid paralysis) by blocking releaseof the neurotransmitter acetylcholine. Death results from suffocation if this occurs
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