patho exam 3 Flashcards

Question

cholera outbreak in Yemen

Answer 1

worlds worst cholera outbreak 2000 people have died, a quarter of them children more than half a million suspected cases

Answer 2

this is an active system in the bodies immune system. Antibodies are produced against ingested organisums some of which are termed Secretory and released back into the Lumen t attach incoming organisms. Preemptive strike! Mycobacterium tuberculosis is an intercellular pathogen that infects macrophages.

Answer 3

pic a-m- cell pic b- infected by Y. pseudotuberculosis.

Answer 4

motility and methods to stick to cells

Answer 5

mouth, small intestin, bladder? - mucsal surfaces are washed by fluids. Bacteria capable of adhearing to a surface have a selective advantage. - many pathogens have mechanisms of attaching themselves to host epithelial cells. - Specific receptors , diffrent parts of the body infected. Also host specific human strains of the particular bacterial species may not adhere to epithelial cells of an animal and vice-versa.

Answer 6

addvantage to be able to move towards a nutrient source or away from an unfavorable enviroment. - Flagella- ae specialized structures that provide motility - Fimbrie/pill- can be involved in motility

Answer 7

Directe movement of an organism toward ( positive) or away from ( negative ) a chemical gradient.

Answer 8

- same basic structure shared between Bacteria and Archaea. - flagella genes are highly conserved across these 2 domains sugetting motility has **Depp evolutionary Roots.**

Answer 9

Bacteria- Green filamentous bacteria gram positives spirochetes proteobacteria cyanobacteria Planctomyces Bacteroides Cytophaga Themotoga Aqyifex -Archaea halophiles methanosarcina methanobacterium methanococcus T.celer Themoproteus Pyrodicticum -Eukaryota Entamoebae slime molds animals fungi plants ciliates flagellates Trichomonads Microsporidia Diplomonads

Answer 10

polar lophotrichous peritrichous

Answer 11

- some can move at 60 cell length /sec - cheetah only 25 lengths /sec - Polar flagellated organisms -rapid , spinning motion - Peritrichously and lophotrichous flagellated organisms move in a straight line -

Answer 12

- **Regulation genes**- for synthesis and control - **structural proteins**- make up flagella itself - **Chaperones proteins**- mediate export of flagella proteins through cytoplasmic membrane to the outside of the cell to construct the flagellum itself.

Answer 13

- **Base** and **Filament**

Answer 14

several "rings" make the basal body -an outer **L** in **L**PS, **P** in Peptidoglycan, **MS** and **C** rings ar3e located in **c**ytoplasmic **M**embrane and **C**ytoplasm.

Answer 15

lack outer membrane and so **no outer L Ring**

Answer 16

1000-1200 protons/ revolution - protons flowing through channels exert electrostatic forces on helically arranged charges on the rotor proteins. - Attractions between + and -ve ions cause the base to rotate 1200 protons/revolution

Answer 17

- at the base the motor that rotates the flagella is anchored in the cytoplasmic membrane and cell wall. - Acchored int eh cytoplasm membrane ar ethe **Mot** and **Fil** proteins acting as the motor **and switching ( reverse) mechanisms.** **-Motion from te basal body- Proton Motive Force,-** protons move across the cytoplasmic membrane through the **Mot complex** (1000-1200 ions per revolution)

Answer 18

many belive the flagella is not evolution but intelligent design

Answer 19

prokaryotes are too small to sense a gradient along the single cell insted sense what they passed through a few secounds before movement /direction therefor apper a little erratic - without a gradient, cells move in a random fashion - **-Smooth "runs"** swimming forward and **" tumbles"** where cell stops and jigs about, changes direction then "runs" in a new direction.

Answer 20

- in gradient, fewer tublems and more runs and bacteria moves towards attractant or way from a repellant. - Anticlockwise forward motion, clockwise the bundle of flagella pushes apart, foward motion cease and cells tumble. - Polar flagellated cells, reverse direction of rotation results in backward motion.

Answer 21

sensory proteins in the cytoplasmic membran sense the chemical gradients - changes in the enviroment are sensed at both genetic and biochemical levels. - Interact with cytoplasmic proteins to affect flagellar motor direction.

Answer 22

surface structures - Fibriae - Pilli - Capsules - Slime layers - Specialized proteins

Answer 23

Rod shaped protein structures, adhesins that diffre in thickness and length ( often on Gr -ve organisms) -**Fimbriae**- shorter, thinner structures **-Pili-** longer, thicker structures -orderly array of single subunits called **Pilin** packed in a helical way to form a cylindrical structure.

Answer 24

-many pathogens have a two- step process of the pili making initial contact. The pile retract and "pull" the bacteria close to the host cell where the adhesins take over and the pili depolymerize to make a much more strong bond.

Answer 25

-once thought that pili were metabolically inert. Now it appers that the attachment of Pili envokes a whole range of "gene switching" of virulence genes. The action may take the form of conformational changes in the pili tips upon binding (proteins E,F,G).

Answer 26

flagella- long tails fimbriae- smaller hairs

Answer 27

- additional proteins -ushers interact with chapreons and guide the subunits to the cell surface. - present in the periplasm , prevent the pili from folding into their final configuration until ready to be extruded from the out membrane - this is called the **Chaperone Usher system** - finally a periplamic **Protein H** signals the end of the extrusion process. how the bacteria mesures the length of decided what the final should be is not yet known.

Answer 28

1. secrection and **Specialized tip proteins (E,F,G)** cross the inner membrane and into the periplasmic space. 2. in addition to the actual pilus proteins there are a number of proteins that help in construction of the pilus. - **Usher** **-scaffold structure C** **-Chaperones** **-**the main shaft is assembled from **Protein (A)**

Answer 29

**Twitching motility.** - rapid extension/ reaction enables the cell to "crawl" along the surface. **Key colonization factor**-in Nesseria menigitidis ( bacterial meningitis) and Vibrio Cholerae ( cholera) **Avoid host defenses .** -Pili break easily when bound by host aantibodies can break away (E,F and G protiens). Also **Once the body recognizes the pili another type of pili with a diffrent tip is produced by the bacteria.**

Answer 30

-**oral strains able to adhere and form biofilms** strep, salvivarius, Strep, gordonii, Strep. oralis, Strep. Parasaguis and Actinomyces naeslundii. - short, thin, rod- like fimbriae. - covalent attachment of sbunits to each other and to peptidoglycan cell wall. - **Biofils can be thought of as a virulence factor.**

Answer 31

are matrices of organisms where gradients of nutrients exist. **-homoserine lactones-**involves communication between cells- **Quorum sensing**

Answer 32

- reduced metabolic levels - resistance to antibiotics - reduction to predation - pseudomonas aeruginosa

Answer 33

- important in pre-infection and establishing colonization/ disease. - **Pseudomonas aeruginosa** - in cystic fibrosis **-Legionella pneumophillia** in Legionnaire's disease **-Streptococcus, Bacteroides, Fusobacterium** in dental plaque (endocarditis) **-S.epidermidis, Enterococcus facalis, E. coli, Proteus mirablis, P. aeruginosa** -**K. pneumoniae-** medical catheters.

Answer 34

colonization organisms.

Answer 35

- is part of the immune system that helps (complements) the ability of antibotics and phagocytic cells to clear microbes and damaged cells from the host organisum **Promotes inflamation** - 3 patheays involved but all lead to the formation of the **Membrane Attack Complex (MAC)**

Answer 36

antibody controlled -host may produce antibodies that bind capsule providing sites both for phagocyte binding and activation of complement.

Answer 37

**-IgG and IgM antibodies bind antigens** that become cross-linkage by multiprotein **C1.** **-** this antiody -antigen complex leads to **C2 and C4** binding at an adjacent membrane. -

Answer 38

- controlled by serum protein - Serum protein **Properdin** binds to bacterial cell surface. - this membrane bound complex binds C3 and **protein factor B** - catalyzes the formation of **C5-9MAC** leading to cell destruction as demonstrated in the classical pathway.

Answer 39

**Mannose Binding Lectins** present on the cell walls of bacteria.

Answer 40

- membrane damage and cell lysis - recruits the C6-C9 proteins

Answer 41

- many prokaryotes secrete a loose, unstructured network of polysaccharide/protein-carbohydrate. - may be rigd (capsule) or flexible (slime) thick or thin. - **Evade complement and phagocyte- mediated killing.**

Answer 42

- enteropathic (disease of the intestine) e. coli - extracellular polysaccharide - Mucoid colonies

Answer 43

- protect from host inflammatory response (complement activation and phagocyte-mediated killing) - Interferes in "alternative pathway"? - can prevent binding of the **B protein** and activation of the **C3** complement and the **MAC ( membrane Attack Complex)**

Answer 44

1. **Serum protein** **-Properdin** binds to cell surface. This membrane bound complex binds C3 and **Protein factor B** 2. -catalyzes the formation of **C5-9MAC** leading to cell destruction as demonstrated in the classical pathway.

Answer 45

Serum resistant - although some C3b (opsonizing) can attach under the loose capsule, the capsule can prevent contact with phagocyte receptors. - MAC may form too far way from membrane due to capsule that forms a physical barrier and therefore no bactericidal effect.

Answer 46

- in some instances, proteins can diffuse through the capsule layer and still cause complement activation - so just having a capsule or slime layer dosent protect pathogens ompletely. - can be used for vaccines and have been very successful against a number of pathogens. ex. Haemophilus influenzae type b

Answer 47

meningitis is an infection of the fluid of a persons spinal cord and the fluid that surrounds the brain. - **Viral meningitis is generally less severe** and resolves without specific treatment, while **bacterial meningitis can be quite severe and may result in brain damage, hearing loss, learning disabilities and death.** - Before the 1990's **Haemophilus influenzae type b** was the leading cause of bacterial meningitis, but new vaccins being given to all children as part of thier **routine immunizations have reudced the occurrence of invasive disease due to H. influenzae.** **-**leading causes are **Streptococcus pneumoniae** and **Neisseria meningitis** are leading causes of bacterial meningitis.

Answer 48

-non immunogenic or autoimmune problems

Answer 49

**S.pyogenes-** Hyaluronic acid (mammalian polysaccharide) **Neisseria meningitdis**-Sialic acid (SA) (mammalin glycoprotein) **Attachment of sialic acid** ( and othr substances) to LPS O-antigen prevents formation of **C3 convertase.** **-**SA- can also hide mannose antigens on the surface of host cells or bacteria from mannose- binding lectian ( 3rd pathway of complement system) of host immune cells.

Answer 50

changes in the length of the LPS-O antigen side chains this mechanism is not well understood.

Answer 51

**s.aureus**-protein A **Step. pyogenes**- protein G

Answer 52

making the bacteria more sticky. so phagocytes get trapped and kill the cell

Answer 53

singal monomer complement binding site phagocyte receptor binging site binds to antigen on forgin materia

Answer 54

5 monomers=10 binding sites more efficent cause clumping action-easier for macro phages to degrade bacteria

Answer 55

IgG clumping factor binds fibrogen collegen binding protein attachment to extracellular matrix proteins fibrogen binding protein capsule

Answer 56

enhanced 10-fold by antibody binding 10-fold by c3b fixation.

Answer 57

produce enzymes that specifically degrads C5a found in gram +ve's -produce toxins that kill ohagocytes inhibit migration or reduce the oxidative burst ,odification of LPS so the immune response is not activated -H. Pylori

Answer 58

pus forming bacteria dead phagocytes make up large part of pus

Answer 59

produces pigmented compounds called **Carotenoids** neutralized the "oxidative burst"

Answer 60

intercellular pathogen uses cell wall **Glycolipids** to scavenge toxic oxygen compounds, remove hydroxyl radicals and superoxide anions.

Answer 61

cytotoxin produced by some intracellular pathogens such as Stap.aureus and Strep. pyogenes -organisums are ingested but then released as phagocytes are killed dead phagocytes make up a large part of pus

Answer 62

polysaccharide/protein coating -Encapsulated bacteria aqre often highly resistat to phagocytosis prevents adherence of phagocyte to the bacteial cell killing action of the MAC

Answer 63

capsule 10 cells can kill a mouse in a few days non- encapulated strains are a virulent.

Answer 64

cytokines /chemokines and complement guide the phagocytes to the infection -prime these cells for activation only at the site of infection. 118

Answer 65

**involved in cell signaling** **cytokines -include chemokines, interferons, interleukins, lymphokines, tumor necrosis factor.** -produced by a broad range of cells including immune cells like macrophages, **B lymphocytes, Tlymphocytes and mast cells** as well as endothelial cells and fibroblast.

Answer 66

free radical during infection cytokines trigger monocytes and macrophages to produce Nitric Oxide. - attacks bacterial metalloenzymes, proteins and DNA - NO also combines withsuperoxide the synergy is more reactivve =**Peroxynitrite -** that oxidizes amino acids causing protiens to denature NO- is toxic to both bacteria and human cells

Answer 67

- a non specific reaction to noxious stimuli such as toxins and pathogens -redness, sweling and pain - mediated by **Cytokines** **-**an bnormal upward deviation from 37C - may be caused by externally induced pyrogenic agents from bacteria (LPS) (fever inducing/heat generating) or **Endogenous Pyrogens-released from leukocytes**

Answer 68

are a group of cytokines interlukins lL-1,IL-6, Tumor Necrosis Factor (TNF-a)

Answer 69

fever/heat generating

Answer 70

continuous fever inter mittent fever relapsing fever

Answer 71

body temperature remains elevated over 24 hour period; \<1 C variation

Answer 72

body temperature shifts between normal and raised throught 24 hour period; period characteristic of most infectious diseases

Answer 73

fever returning after an infection is reestablished.

Answer 74

swelling redness pain heat loss of function these signs are due to the changes in blood vessel function

Answer 75

to bring phagocytes to the injered area to isolate destroy inactivate the invader remove debris prepare subsequent healing

Answer 76

phagocytosis by macrophages dilation an incread permeability Containment of bacteria nad forign matter leukocyte proliferation and migration continued activity of recruited leukocytes.

Answer 77

up regulate host responses

Answer 78

stimulate the killing active of PMNs

Answer 79

trigger the release of monocytes and PMNs (Polymorphonuclear leukocytes /neutrophiles) from the bone marrow onto circulation.

Answer 80

rolling motion

Answer 81

stimulate endothelial cells to produce selectins that bind loosely to the surface of PMNs and other cells causing them to slow.

Answer 82

``` (cytokine) –stimulate PMNs to produce integrins that in turn stimulate more cytokines called intracellular adhesion molecules (ICAMS) to generate a tighter attachment of above cells (Margination). ```

Answer 83

``` (Transmigration) assisted by platelet-endothelial cell adhesion molecule (PECAM). ```

Answer 84

activate the PMNs oxidative burst so enabling the full killing capacity of the cell.

Answer 85

also triggers mast cells to produce additional vasoactive compounds ?

Answer 86

slowing and stopping of polymorphonuculear leukocytes (PMNs)

Answer 87

PMNs cross the endothelial wall into the deeper tissue.

Answer 88

1. expansion of capilaries to increase blood flow 2. incr3ease in permeability of the micovascular structure to allow escape of fluid 3. exit of leukocytes from the capillaries and response to infection (pus)

Answer 89

pattern of recognition molecules are toll like receptors TLRs These receptors recognize structures on bacteria -pathogen associated molecular patterns -LBP-Lipopolsaccaride binding protien-produces by hepatocyte intestinal epihelial cells- ciculates in serum

Answer 90

when the phagocytes are sucessful in eliminating the invading bacterium, a second set of cytokines begin to predominate.

Answer 91

down regulate production of TNF-a and reduce the kiling activities of phagocytes and returning the sytem to its normal inactive level.

Answer 92

IL-1, IL6, IL-8, platelet activating factor (PAF) and TNF-a (killing action of phagocytes)

Answer 93

IL-4, IL-10, and IL13

Answer 94

the inflammatory processes fails to localize the pathogen and reaction becomes widespread.

Answer 95

- gr -ve's Salmonella or E.coli- ruptured or leaking boel releasinf organisms into the intra peritoneal cavity or the bloodstream - gr- +ve's Staphlococcus aureus and Streptococcus pyogenes-burns - production of endotoxins

Answer 96

1. systemaic inflammation response syndrom (SIRS):- temos over 38C higher and respitoratory rates. Unusally high or low neutrophile count 2. sepsis- organ dysfunction and very low blood pressure. severe sepsis- organ dysfunction and very low blood pressure 4. septic shock - very low blood pressure despite fluid administration.

Answer 97

- vascular resistance and blood pressure drop despite normal or high cardiac output. - essential organs denied oxygen and nutrients. - resulting failure of the kidneys , heart , brain, and lungs is the cause of death- multipe organ dysfunction (failure)

Answer 98

* More than 1.5 million people get sepsis each year in the U.S * About 250,000 Americans die from sepsis each year * One in three patients who die in a hospital have sepsis

Answer 99

- LPS - Inflammatory cytokines - prostaglandins

Answer 100

prostaglandin receptors

Answer 101

\* constriction or dilation in vascular smooth muscle cells \* aggregation or disaggregation of platelets \* sensitize spinal neurons to pain \* regulate inflammatory mediation \* control cell growth \* control hormone regulation

Answer 102

Coagulation Cascade System -This depletes the blood of essential clotting factors and leading to small hemorrhages (?) in many parts of the body adding to hypotension and organ damage. -**clots plug capiillaries----\> blackish or reddish skin lesions.---\>DIC\_ disseminated intravascular coagulation.**

Answer 103

past treatment centered on glucocorticoid treatment (corticosteroids-steroid hormones (down regulate cytokines)- not effective. •Antibodies and compounds active against TNF-a are being tested, not promising. •Anti-cytokine agents may be more promising. •Early antibiotic treatment - expensive tests, take time, delays leads permanent damage to vital organs. •Many types of bacteria can cause septic shock -no single antibiotic / or test is effective. -require more tests to identify specific pathogen, but costs $$$

Answer 104

1. Oxygen administration and airway support. 2. Volume resuscitation (serum /plasma /artificial blood). 3. Early antibiotic administration. 4. Rapid source identification and control. 5. Support of major organ dysfunction.

Answer 105

very specialized group of pathogens, some are obligately parasitic ( i.e cannot survive outside the host) - normally functional genes are not required as host cell provide all nutrients ect. reduction in genome size.

Answer 106

4 million base apirs with about 3000 genes

Answer 107

Bacterial surface proteins called invasins causes polymerization and depolymerization of actin that form and mediate the cytoskeleton producing pseudopodia-like structures that mediate engulfment of the bacterium forming a vacuole.

Answer 108

Legionella pneumophila, Mycobacterium tuberculosis, and Salmonella typhimurium.

Answer 109

• disrupt the surrounding vacuole membrane and escape into the cytoplasm • multiply and move about by directing local actin polymerization at one end of the bacterium, a process called **‘actin-based motility’.** ## Footnote **---Listeria monocytogenes, Rickettsia, Shigella.**

Answer 110

causes bacillary dysentery ( sever bloody and muscous diarrhea) or water. the bacteria are highly infectios since as few as 10 tp 100 microorganisms are sufficient to cause disease -unlike many pathogens **have no adheareence factors** **- in the colon and rectum- shigella translocate through the epithelial barrier via M cells** invading the resident macrophages, escape from the phagosomes into the cytoplasm where they multiply and induce rapid cell death.

Answer 111

Shigella- when Shigella comes into contact with epithelial cells, the **Tpe III SECRETION systems (TTSS)** is stimulated and delivers **Effectors (IcsB)** into the host cells which play roles in camouflage against phagocytic recognition. Focus of both Genomic and Protemics research

Answer 112

- Protein synthesis stopped - Cell wall integrity affected - Nerve impulses interrupted

Answer 113

Kill neutrophils and macrophages kill host cells to release iron stores or carbon (nutritional) sources.

Answer 114

toxin produced when in food prior to ingestion. - commen in canning proccess •Bacteria form spores, pass through the GI tract and do not colonize the GI tract or enter tissue. •Toxin attacks neurons causing paralysis and death (collapse of respiratory system).

Answer 115

C. botulinum (C & D) Corynebacterium diphtheriae -The example of Botulinum toxins suggests this is not the complete story and toxins may have other physiological role in the bacterium………. - Regulation of cellular or phage function - cell-cell signaling

Answer 116

Some toxins are not excreted - rather accumulate and released on cell lysis - or injected directly into host cells therefore bypassing extracellular phase

Answer 117

1. Cytotoxins: - can have a more general action and attack a variety of cells 2. From disease or bacteria: - cholera, shiga, diptheria, tetanus 3. Type of cell or organ affected: -neurotoxin, leukotoxin, hepatotoxin, cardiotoxin brain leuckocytes liver heart

Answer 118

- adenylate cyclase, (Bordetella pertussis –whooping cough) - lecithinase (Clostridium perfringens –gangrene)

Answer 119

- Botulinum – A-G

Answer 120

-Exotoxin A (Peudomonas aeruginosa)

Answer 121

- E.coli 0157:H7 –shiga-like, verotoxin (culture cells) O157 means that this was the 157th different kind of O antigen found in E. coli. The antigens on the tail, or flagella are called H antigens. H7 means that this was the 7. Most E. coli strains harmlessly colonize the gastrointestinal tract of humans and animals as a normal flora. However, there are some strains that have evolved into pathogenic E. coli by acquiring virulence factors through plasmids, transposons, bacteriophages, and/or pathogenicity islands. These pathogenic E. coli can be categorized based on serogroups, pathogenicity mechanisms, clinical symptoms, or virulence factors. Among them, enterohemorrhagic E. coli (EHEC) is defined as pathogenic E. coli strains that produce Shiga toxins and cause hemorrhagic colitis (HC) and the life-threatening sequelae hemolytic uremic syndrome (HUS) in humans. E. coli O157:H7 is the most frequently isolated serotype of EHEC from ill persons in the United States, Japan, and the United Kingdom.

Answer 122

endotoxin-LPS - structure of Gr-ve cell wall, recognized by the ummune system - entrotoxin used specifically for toxins in the small intestin producing diarrhea or vomiting enteric symptoms - food posing - e.g. Sty. aureus, C. perfringens, B. cereus, Camp. jejuni - intestinal pathogens - ibrio cholera, E. coli, Salmonella enteritidis

Answer 123

A repetiitive glycan polymer - contained within an LPS is referered to as the **O antigen, O polysaccharide or O side chain of the bacteria**

Answer 124

**is exposed on the very outer surface of the bacterial cell,** and, as a consequence, **is a target for recognition by host antibodies.**

Answer 125

the core domain always contains an oligosaccharide componet that attaches directly to Lipid A and Commonly contains sugars.

Answer 126

is a phosphorylated glucosamine disaccharide decorated with multiple fatty acids. These hydrophobic fatty acid chains **anchor the LPS into the bacterial membrane,** and the rest of the LPS projects from the cell surface. The lipid A domain is responsible for much of the toxicity of **Gram-negative bacteria.** When bacterial **cells are lysed by the immune system, fragments of membrane containing lipid A are released into the circulation, causing fever, diarrhea, and possible fatal endotoxic shock** (also called septic shock). The Lipid A moiety is a very conserved component of the LPS

Answer 127

the leading cause of bacterial food poisoning, caused by an Campylobacter jejuni, most often spread by contact with raw or undercooked poultry. -Campylobacteriosis. Low multiplicity number --- diarrhea, fever, abdominal pain, cramping, nausea and vomiting -- but with campylobacter, fever is typical and the diarrhea is often bloody.

Answer 128

Flagella Mucin has been found to be a positive chemotaxin for C. jejuni which is compatible with the bacteria’s colonization of the intestine where there is abundant mucus. -Adhesion and invasion are important virulence factors for colonizing the host's intestinal cells. -C. jejuni also contains lipopolysaccharides (LPS) in their outer membrane.

Answer 129

bind to host surface but are not translocated into the cell

Answer 130

macrophages and T-cells and stimulate large amounts of toxic cytokines.

Answer 131

cytikine storm -cell singlaing protiens that are secreaed by numous cells and are a catagorey of sinalikng molecules used extensively in intercellular communication.

Answer 132

Cytokine stoms- pandemic. Deaths were weighted more heavily towards people with healthy immune systems, due to its ability to produce stronger immune responses, like increasing cytokine levels. • Nausea, vomiting, malaise, and fever Staphylococcus aureus (enterotoxin) and Streptococcal infections 200

Answer 133

1. Proteins that form channels in the membrane -Osmotic strength of the cytoplasm is higher than the environment - breach in membrane causes water to rush in and the cell swells and ruptures. 202

Answer 134

Streptococcal Streptolysin O -affects the sterols of the host cytoplasmic membrane

Answer 135

-lyse white blood cells

Answer 136

-disrupts smooth muscle in blood vessels but also toxic to many cell types

Answer 137

remove the charged head

Answer 138

cleave at other sites again to destabilize the cell membrane. - ex Eg. Phopholipase, hemolysin, cytotoxin.

Answer 139

hemolysis cytotoxin phopholipase blood agar assay- C. perfringens a-toxin Toxin can enter bloodstream and damage the kidneys gas gangren

Answer 140

Active (enzymatic) (A) and Binding (B) portions. • Simple (single polypeptide) or compound (multiple subunits). proteolytic cleavage occurs when the A portion is internalized and activated when the disulphide bonds are broken. (B) portion is very specific -Binds to carbohydrate moiety of a host cell glycoprotein or glycolipid (A) portion is less specific and can kill several types of cell if it can gain entry into the cytoplasm.

Answer 141

• Binding of B – leads to A and B being translocated through host membrane into the cytoplasm via Endocytosis or direct translocation forming a vesicle. • Acidification of the vesicle results in A becoming disassociated from B, entering the cytoplasm and traveling to the target and exerting its toxic effect. Although different cells may be attacked the mode of action of the toxin is the same.

Answer 142

Characterized by peeling skin, staphylococcal infection. **begins with a fever and redness of the skin, followed by the formation of a fluid-filled blister that ruptures easily.** Eventually, **the top layer of skin may begin to peel off in sheets.** Staphylococcal scalded skin syndrome mostly affects infants, young children and individuals with a depressed immune system or renal insufficiency. The disease can be life threatening. Treatment usually requires hospitalization, often in the burn unit of the hospital

Answer 143

**Protein synthesis is inhibited. • ADP-ribosylation** of host cell proteins ADP-ribosyl group is removed from NAD and covalently attaches to the host protein inactivating it or causing it to behave abnormally.

Answer 144

**Acts on elongation factor-2** –which normally brings an amino charged tRNA to the ribosome for incorporation into a peptide -prevents protein synthesis

Answer 145

``` ADP-ribosylates an enzyme that controls AMP and ion flow leading to massive water loss (diarrhea) ```

Answer 146

A) **subunit cleaves a host cell rRNA molecule, which prevents the ribosome carrying out translocation of proteins.** -Protein synthesis is terminated

Answer 147

• part of the outer portion of the cell wall of Gram negative bacteria • endotoxin consists of polysaccharide **(immunogenic)** and lipid part of the LPS, is **Lipid A which is the toxic component** • released upon cell lysis and cell multiplication •LPS binds to LPS-binding protein and interacts with Toll-like receptors (TLRs) • Stimulate macrophages to release pro-inflammatory cytokines in very high concentrations

Answer 148

chills, fever, weakness, endotoxic /septic shock and even death

Answer 149

-Factor XII **-Disseminated intravascular coagulation (DIC)** results in lower blood pressure and blood supply to vital organs and accumulation of fluid in the lungs **Acute respiratory distress syndrome**

Answer 150

**Bordetella pertussis -Whooping Cough** **Bordetella Tracheal Cytotoxin (TCT)** -small molecular weight glycopeptide part of its PG, - Ciliostasis ? - Release of cytokine Iinterlukin-1 -arrest of ciliary movement Without ciliary movement, coughing becomes the only way to clear the airways of mucus, bacteria and inflammatory debris -triggers violent coughing -susceptible to secondary infections and can lead to death.

Answer 151

Cellular damage associated with TCT is thought to be a result of increased levels of nitric oxide (NO) secretion by mucosal cells as part of an innate defense. In humans, peptidoglycan recognition proteins appear to bind with TCT and consequently induce the Tumor Necrosis Factor Receptor (TNFR) pathway. - cytokine secretion - acts as a pyrogen -a substance, typically produced by a bacterium, that produces fever when introduced or released into the blood.

Answer 152

Lipid-like toxin –**cytotoxic and immunosuppressive properties** **Mycobacterium ulcerans** Emerging human pathogen Reservoir – aquatic insects **Buruli Ulcer –** Destructive effects on the skin, soft tissues and bones. –Central/West Africa, Central and South America, Asia and Australia. 237

Answer 153

such as a small scratch in water or insect bite. -toxin is secreted in vesicles -inhibits uptake by phagocytes but can survive if phagocytized M. ulcerans turns off the mycolactone synthesis during the intramacrophage growth. Can cover up to 15% of the body if untreated Even in advanced stages there is **little inflammation and pain!** -lifelong disability -cluster of 3 giant biosynthetic genes-**polyketide synthases** **infection of subcutaneous fat,** resulting in a focus of necrotic (dead) fat containing mycobacteria in characteristic spherules formed within the dead fat cells. **Skin ulceration is a secondary event.**

Answer 154

terium diphtheriae, Gr. +ve, non-sporeforming, nonmotile, aerobic, club-shaped rod. -Epidemiology and Pathology: Severe respiratory condition that usually infects children. But due to immunizations now shifted towards the elderly. BUT Preventable and treatable

Answer 155

Humans only known reservoir. • Diphtheria is a serious disease, with fatality rates between 5% and 10%. • In children under 5 years and adults over 40 years, the fatality rate may be as much as 20% 247 George Washington is thought to have died of this at the age of 67

Answer 156

Diphtheria was once a greatly feared illness in the United States. **1920s**, there were 200,000 cases of diphtheria each year with approx. **15,000 deaths.** Because of widespread immunization and better living conditions, **diphtheria is now rare in the United States** (during 1998-2004, seven cases of respiratory diphtheria were reported to CDC). However, surveys have found that immunity decreases with age, and only 30% of U.S. adults age 60-69 years are protected against diphtheria. This is a concern because the disease continues to occur in other parts of the world • 1980 and 2000 - US. 52 reported cases of diphtheria between **•Diphtheria–Pertussis–Tetanus (DPT) vaccine** is recommended for all school-age children

Answer 157

After the breakup of the former Soviet Union, vaccination rates fell, and large outbreaks of diphtheria began in 1990 in the Newly Independent States. From 1990 to 1998, more than 150,000 people got sick from diphtheria and more than 5,000 people died.

Answer 158

-colonization of throat and tonsils. Inhalation of airborne droplets. Grayish membrane called the **pseudomembrane (fibrin (protein involved in blood clotting),** dead host cells, inflammatory cells and bacteria) forms in the throat extending to the lungs. • Pseudomembrane may block the passage of air, **death is from combination of partial suffocation and tissue destruction by the toxin.**

Answer 159

club shaped rods - swollen or bull neck - also present as a skin disease • **Toxin enters the bloodstream, but bacteria remain in the throat.** • Untreated – irregular heartbeat, difficulty in swallowing, stupor, coma indicative of internal damage to organs. • toxin causes systemic damage to the heart, kidneys, liver and adrenal glands. -

Answer 160

B - consists of two subunits Receptor binding region Translocation region A - Catalytic region • **Toxin B subunit binds to host cell receptor** identified as **heparinbinding epidermal growth factor (HB-EGF) and taken up in an endocytic vesicle.** • Epidermal growth factors are important to may cell types (particularly heart and nerve) as signals for growth and differentiation. • **toxin comprises 5% of total protein!**

Answer 161

endocytosis -pH drops to 5 and amino acids are protonated making them less hydrophilic. • Conformational change, partial unfolding of the A-B chains exposing hydrophobic regions. Insertion into vesicle membrane.

Answer 162

Acts on elongation factor-2 –protein synthesis -Turnover of EF-2 is very slow and only 1 molecule per ribosome… Extremely potent, 1 toxin molecule can kill a host cell.

Answer 163

20 dog team to deliver diptheria antitoxin -1,049 miles in 9–15 days from Anchorage to Nome.

Answer 164

use for C. diphteheria - Loefflers medium- selective-

Answer 165

antitoxins can be used to neutralize the toxin (passive immunization) - derived from horse serum

Answer 166

Highly effective vaccine D**TaP (diphtheria, tetanus, acelluar pertussis).** • Made by treating the exotoxin with formalin yielding an immunogenic **toxoid** preparation. • However it is not the active component that is targeted…… Binding of antibodies that bind (B) and physically interferes with binding to host cell hence preventing internalization of the (A) chain that leads to toxic effect.

Answer 167

vibero cholerae- Gram Neg curved rod - sever diarreal disease - Contaminated water, raw shellfish and raw vegetables -Blood, Na+, K+ HCO-3 (electrolytes) and V. colerae -

Answer 168

Adequate water treatment / safe drinking water

Answer 169

Electrolyte replacement therapy Simple, effective and inexpensive Intravenous or oral liquid Glucose, NaCl, KCl, NaHCO3 – mortality down to 1%.

Answer 170

**Clostridium botulinum, Gr. +ve, sporeforming, obligative anaerobic rod.** • Normally found in soil and lake sediments • cause death in humans in doses as small as 0.05–0.1 μg

Answer 171

-Severe food poisoning, often fatal due to paralysis of lungs (suffocation) and heart muscle. Not an infection as more intoxication ? Preformed, **toxin-mediated**, so more of a chemical attack not by the presence of the actual organism toxin is so deadly, in fact, that simply **sniffing i**t at a dose of **13-billionths of a gram can be lethal.**Worse,**an injection of only 2-billionths of a gram can kill. For comparison, arsenic, one of the most popular fatal poisons, is lethal at only one-tenth of a gram!!**

Answer 172

**In the United States, an average of 145 cases are reported each year.** Of these, approximately 15% are foodborne, 65% are infant botulism, and 20% are wound.

Answer 173

**ingestion of foods not cooked correctly after processing** - canning, plastic vacuum packed meats/fish, honey etc • If the food is cooked correctly, boiling 10-15 mins inactivates toxin. • **Toxin absorbed from the intestines into the bloodstream.** • Specific for neurons attacking **peripheral nerve endings.**

Answer 174

Clinical observations, localized paralysis (impaired sight and speech), neurological problems- within 4-36hrs after ingestion

Answer 175

•Prevention- correct preparation of food •Controls over canning and preservation methods –especially in rural communities (home canning!). •Early diagnosis – antitoxin can prevent the disorder from worsening, but recovery still takes many weeks 286

Answer 176

Transient colonization: Infant Botulism: **The infant intestinal tract often lacks both the protective bacterial flora and the clostridiuminhibiting bile acids found in normal adult intestinal tract.**Consequently the infant intestinal tract is more susceptible to colonization by toxin producing Clostridium botulinum species. **Spores ingested -growth of bacteria in GI tract** Nausea and vomiting not seen but constipation seen. Absorption is slower from colon but death can occur. 288

Answer 177

deep wounds can provide an anaerobic environment, due to tissue damage that cuts off the bloodstream. Enables **the growth of the organism prior to toxin production.**

Answer 178

**Botulism can be treated with an antitoxin which blocks the action of toxin circulating in the blood.** Antitoxin for infants is available from the California Department of Public Health, and antitoxin for older children and adults is available through CDC.If given before paralysis is complete, antitoxin can prevent worsening and shorten recovery time. Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enemas. -**Wounds** should be treated, usually surgically, to remove the source of the toxin-producing bacteria followed by administration of appropriate antibiotics. Good supportive care in a hospital is the mainstay of therapy for all forms of botulism. -**Respiratory failure and paralysis** that occur with severe botulism may require a patient to be on a breathing machine (ventilator) for weeks or months and may require intensive medical and nursing care. -After several weeks, **the paralysis slowly improves as axons in the nerves are regenerated.**

Answer 179

-**8 related toxins A-H** most potent biological toxin known. Types A and B cause most infections. -1mg can kill 1million guinea pigs. death in humans in doses as small as 0.05–0.1 μg • At least two coded by lysogenic phages, C & D. • Type G may be plasmid borne. 294

Answer 180

- Botulinum toxin (Botox)-neurotoxin, - C2 and C3 toxins (ADP-ribosylation) – protein synthesis.

Answer 181

derivative toxin- • Activation by proteolytic cleavage by either protease produced by the clostridia or gastric proteases. • Amino terminus of the “H” chain causes formation of a endocytic vesicle in the neuronal membrane allowing the “light chain” to enter the cell.

Answer 182

-nerve pulse to the muscle is through acetylcholine interaction with receptor. Toxin **binds to presynaptic membranes** on the termini of the **stimulatory motor neurone** at the neuromuscular junction, **blocking release of Acetylcholine (Neurotransmitter).** • Nerve receives excitatory signal but contraction is prevented, causing **flaccid paralysis.**

Answer 183

are chemicals that are used to relay, amplify and modulate electical signals between a neron and another cell.

Answer 184

Organism: **Clostridium tetani, Gr. +ve, motile, spore-forming, anaerobic rod. Found in soil (and GI tract of animals).** Epidemiology and Pathology: Serious life threatening, but preventable by immunization. (last decade 473 US cases / 68 deaths)

Answer 185

Diagnosis based on exposure, clinical symptoms. Culture of organism is variable. • muscles of face and jaw first affected, diagnostic trait ? • Death results from respiratory failure. **Lockjaw**

Answer 186

Treatment of cuts and punctures, “booster” tetanus shot. **Antitoxin** made in horses, neutralizes toxin as it is released. Penicillin, sedation. • Effect of toxin is not reversible, recovery depends on whether new axonal terminals form. Significant mortality. Prevention and Treatment: **• Toxoid vaccine**, very effective.

Answer 187

Major killer worldwide in developing countries. • Infant tetanus in the top 15 of top killers Local customs contribute e.g. packing of umbilical cord with cattle dung.

Answer 188

Opposite to botulism rather than flaccid, a **rigid or “spastic” paralysis** ensues. Contracted muscles cannot relax. 2 toxins combined - oxygen labile hemolysin **(tetanolysin)** - plasmid borne, heat labile neurotoxin **(tetanospasmin).**

Answer 189

On contact with CNS, toxin is transported through the motor neurons back to the spinal cord. • **Binds to ganglioside lipids at the terminus of the inhibitory interneurons, • Cleaves synaptobrevin, blocks release of glycine. • Inhibitory neurotransmitter (glycine),**binds to receptors on the motor neurons and allows relaxation of muscle.

Answer 190

**Gramstain-positive, rod-shaped, anaerobic.•Spore forming.** Commonly found in the intestinal tracts of humans and animals. Ubiquitous in nature. Produces **Clostridium** **perfringens** **enterotoxin** **(CPE).**

Answer 191

• **Major cause of food poisoning** **in the United** **States and Great Britain.** Spores are extremely resistant to heat and other means of food preservation. • cpe encoded chromosomally. • **CPE released upon cell** **lysis** **in the final stage of** s**porulation**

Answer 192

-causes 80-95% of cases of gas gangrene. Mortality from traumatic gas gangrene is 25%, mortality from non-traumatic gas gangrene caused by the more aerotolerant organism Clostridium septicum ranges from 67-100%. Gangrene shows the full potency of a virulence factor !!

Answer 193

**is aerotolerant and infects normal, healthy tissue** (unlike C. perfringens) and therefore may be the deadlier of the two Clostridia.

Answer 194

t least 7 toxins produced

Answer 195

-high mortality even with early treatment. Toxins disrupt membranes causing cell lysis ….? 1. releasing nutrients for the bacteria to utilize 2. creates larger area of dead tissue that becomes anoxic (anaerobic) for the growth of this organism. 324

Answer 196

Growth of vegetative cells, **alkaline conditions of small intestine stimulates Sporulation, t**riggering production of the enterotoxin. Toxin also kills cells producing anaerobic condition to allow spores to germinate

Answer 197

• Improperly prepared/stored food. • Short doubling time (10-15 mins) – rapidly reaches pathogenic levels. • A few survive stomach acid inside food particles. • Enter small intestine. • Sporulation -\> release of CPE -\> food poisoning.

Answer 198

Isolation of organism from the GI tract (stools)**, or direct enzymelinked immunosorbant assy (ELISA) to detect enterotoxin in stools** (feces). **Self limiting, treatment with antibiotics is not usually required.** Correct treatment of food, refrigerate food as quickly as possible, low temps inhibit C. perfringens. 330

Answer 199

Develops within a week of trauma or surgery • **Shows full virulence potential of toxins** • life-threatening • Muscle necrosis, shock, renal failure and death within 2 dys of initial onset! • High mortality rate

Answer 200

debridment - removal of dead tissue with maggot therapy -and hyberic oxygen treatment.

Answer 201

**Organism? Clostridium perfringens** Gas gangrene also known as "**Clostridial myonecrosis**”, is a bacterial infection that produces gas in tissues -it is a medical emergency.

Answer 202

-Use of maggots that eat only dead tissue leaving alone healthy tissues. -military surgeons noted that soldiers whose wounds became infested with maggots often survived than soldiers with similar wounds not infested!

Answer 203

attach to human or animal through suckers at each end of its body and then eats its host blood - eat 10-15x thier body weight and do not need to eat again for a year - Hirudotherapy, **-venous congestion due to inefficient venous drainage** - If this congestion is not cleared up quickly, **the blood will clot and arteries that bring the tissues their necessary nourishment will become plugged and the tissues will die.**

Answer 204

Leeches can decompress tissues engorged from bleeding or poor venous circulation • They can remove hematomas (collections of blood) • Once detached, the bite sites continue to bleed, which can promote circulation of the affected tissue. **reducing the swelling in the tissues and promoting healing by allowing** f**resh, oxygenated blood to reach the area until normal circulation can be restored.**

Answer 205

calle hirudin contains a number of chmical compounds useful in medicine -local anesthetic prevents heart attacks and strokes the hindin compound used to prevent blood cloots -bacterium aeromonas hydrophilla aids in the digestion of ingested blood and produces antibiotic that kills tother bacteriqa qnd may cauwse purifacation

Answer 206

has proven to be useful for a number of other conditions including cardiovascular disease, ophthalmology, osteoarthritis and dermatology. Hirudin is also used in the treatment of inflammation of the middle ear. -secretion of a local anesthetic by the leech makes the procedure painless except for the initial attachment phase. They fall off promptly after they have completed feeding. • The hazards include infection, excess blood loss that may require blood transfusion, allergic reactions and….. •

Answer 207

Bacteriophages and Viruses • Target individual bacterial species and not wide spectrum • 1920s fist used as anti-bacterial agents • 1930s Eli Lilly (US) marketed 7 phages –Staphylococcus, Streptococcus and E.coli.

Answer 208

1940 -new impetus to look for alternative antimicobials

Answer 209

Every bacteria known – complementary phage • Extremely specific for individual bacterial species – no cross-reaction, do not infect animal / human cells – resident flora • Self limiting, continue to kill bacteria until all are removed, action ceases and dormant phage are dispersed.

Answer 210

**Grow exponentially- single dose –phage self replicating while bacteria are present.** Antibiotics become diluted and excreted from the body – multiple does long term therapy. • Production simple and relatively inexpensive - under-privileged populations may be served better !? • **No allergic reaction known,** omnipresent - soil, water, plants and humans 387

Answer 211

Phage / virus therapy holds great promise **not only for killing bacteria but as vehicles for drug delivery systems to eukaryotic cells in place of chemotherapy eg. cancer patients etc. –specific cells affected**

Answer 212

Lysins -lyse Gr. +ve cell walls. ? digest the bacterial cell wall for bacteriophage progeny release

Answer 213

High specificity – need to identify bacterial infection prior to treatment. •Bacterial subgroups -antibiotic wide spectrum, phages extremely narrow. “phage cocktails”? •Gene transfer – phages are used to transfer genetic material -antibiotic resistance. •Overcome public concerns of taking “viruses”, past conditioning teaches us that viruses are dangerous in the extreme. -However –probiotic bacteria have led the way to reduce these concerns of taking live organisms.

Answer 214

Protein-based anti microbial substances produced by bacteria •**Ribosomally synthesized peptides** •differ from traditional antibiotics in one critical way: They have a **relatively narrow killing spectrum and are only toxic to bacteria closely related to the producing strain.**

Answer 215

Given the diversity of bacteriocins produced in nature, it is a relatively simple task to find bacteriocins active against specific human pathogens

Answer 216

a reduction in antibiotic use should lead to a slow down in the spread of antibiotic resistance.

Answer 217

produced by Lactic Acid Bacteria used in the production of fermented foods. Because LAB have been used for centuries to ferment foods, they enjoy **GRAS (Generally Regarded As Safe)** status by the U.S. Food and Drug Administration (FDA). ?

Answer 218

- was the first bacteriocin to be isolated and approved for use in foods, specifically to prevent the growth of Clostridium botulinum in cheese in England. By 1988, the FDA had approved its use as a biopreservative for a narrow range of foods, including pasteurized egg products. Today, used as a safe food preservative by over 45 countries, and it is the most widely used commercial bacteriocin and it remains the only bacteriocin that may be added to U.S. foods.

Answer 219

Bdellovibrio bacteriovorus • Gram-negative curved rod • Present in all environments • obligate aerobe • Optimal growth at 28-30 C • Large genome (3.85M bp) • Distinct “attack” phase

Answer 220

gram negaticve bacteria digest nutrients in the periplasm prior to the transport of nutrients onto the cytoplasmBdellovibrio dependent on prey to complete lifecycle • Can attack biofilms • Often studied **attacking E. coli or Pseudomonas** -