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61 Cards in this Set

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What is a virulence factor?

Virulence factors are molecules produced by pathogens (bacteria, viruses, fungi and protozoa) and contribute to the pathogenicity of the organism that enable them to achieve the following: colonization of a niche in the host (this includes attachment to cells)

Name 10 Virulence factors

-Enterotoxins


-Siderophores


-Type 1 fimbriae


-Cytotoxins


-Vi capsule antigen


-Flagellum


-O antigen


-Anti-phagocytic


-endotoxins


-Injectosome

What is Molecular Koch's postulates?

It is a set of experimental criteria that must be satisfied in order to prove that a gene encodes for proteins and products which contribute to the advancement or growth of the pathogen

What does avirulent mean?

It is a non pathogenic or virulent organism

What are the conditions for Molecular Koch's postulates?

-product of gene must induce a immune response


-if it expressed in avirulent species it should be mutated or non functional


-Gene is expressed when pathogen is inside host

How does a bacteria infect a target cell with its toxins?

-attach to host cell surface


-Invade host cell


-Injects effectors into host cells


-Many bacteria are limited to a very specific colonisation site


-They then produce and excrete toxins


-Toxins target specific cell types and cause large scale damage of certain tissues

What is a exotoxin?

It is a toxic protein secreted by an organism


-They work at sites distant from the infection


-Highly immunogenic (provoke immune response strongly)

What is an endotoxin?

-Component of Gram-negative bacterial cell wall released by sloughing (releasing dead tissue) or cell death


-triggers systemic inflammatory response


-Is not very immunogenic (provokes comparatively little immune response)

Which is more toxic, endo or exotoxins?

Exotoxins

What is a toxoid?

a chemically modified (e.g. heat treatment) toxin from a pathogenic microorganism, which is no longer toxic but is still antigenic and can be used as a vaccine.

What is another name for endotoxins?

Lipopolysaccharides

What is the general structure of a endotoxin?

Large moleculses which consist of a lipid and polysaccharide composed of an O-antigen, outer core and inner ore joined by covalent bonds

Where are endotoxins found?

Found in the outer membrane/cell wall of gram negative bacteria

What is a good way to remember a charteristic of exotoxins?

-EXO -toxin, the toxin EXits the cell and is spread around body to cause damage


-ENDOtoxin, is endogenous to the cell wall and stays there

Which are more potent, endo or exotoxins?

-Exotoxins are more toxic than endotoxins

Which has the more general action exo or endo?

Endotoxins are much mroe gneral in their effects and jsut cause fever and inflammation in general.

What two populations are carriers of the cholera bacteria?

Pankton and shellfish

What is a common route of transmission for cholera?

It is either transmitted through contaminatedd water supplies , or through eating shellfish that has filter fed infected plankton. Plankton can commonly be infected by contaminated water or by sewage outlets in the sea

Whati s the name of the bacteria which causes cholera?

certain strains of Vibrio cholerae

what does zoonotic mean?

infectious diseases of animals that can be spread to humans

What is the toxin which causes cholera?

it is known as cholera toxin or choleragen



what is the structure of cholera toxin?

-Is a hexameric oligmer complex made up of 6 protein subunits .one single copy of A subunit and five B subunits.


-B units bind whilst the A subunit activates the G proteins which activate adenylate cyclase


-It is an exotoxin

What is the function of lipolysaccardies (Endotoxin)

tyehy are important for itnteractions with other bacteria and adherence to host cells



What is the core region of LPS full of?

Charged polar groups which maintain impermeabilty to polar compounds

What does loss of teh core region in LPS cause?

increased eprmeabilty to hydrophobic compounds such as antibiotics , detergents and bile salts



What is the function of the lipid A ?

anchors endotoxin to host cell due to its hydrophoic nature



What can be seen in all gram negative bacteria?

LPS

What are the symptoms of endotoxin poisoning?

Endotoxin poisoning is mainly immune based in symtpoms , so fever , blood clotting , decresed immunity , systemic inflammation , multiple organ failure and death can occur from a huge immune response.

What are teh mortality rates for edotoxin poisoning?

30% for early stage


90% for late stage

How can the immune system detect gram negative bacteria?

Via actation of TLR4 etc. by LPS

What is a PAMP? How is it invovled in the immune system?

-it is a pathogen associated molecular pattern


Different toll like receptors recognise different PAMPS


-TLR4 recognises the Lipid A section of the LPS

What does too much LPS cause?

Runaway activation of the immune system , causing acute respiratory distress syndrome and Disseminated intravascular coagulation from activating the coagulation pathway. Overactivation of prostaglandins, interleukins and the complement pathways causes damage to blood vessel endothelium and multiple organ system failure

How common is endotoxic poisoning? Which endotoxic disease is commonly fatal in meningitis patients

There are 102,000 cases with 36,800 fatalities in the UK .

Which bacteria is found in the UTR which causes meningitis?

neisseria menningitidis can sometimes cross the epithelial cells via some unknown trigger and enter the bloodstream. It can then cross the Blood brain barrier and cause widespread inflammation



Why is the mennigitis causing bacteria particularly effective at causing endotoxic shock?

n. menningitidis releases membrane blebs.


organism turns over massive amounts of cell wall during systemic phase


- This results in massive amounts of Lipid A into blood stream, causing endotoxic shock

What is a LAL assay?

It is an extract of bloodcells (amoebocytes) from the horseshoe crab. it reacts with bacterial endotoxin or LPS and coagulates. colour generating reagents cleaved by LAL enzymes can be measured for colour development, quantifing the amount of toxin in a sample

What are the Clostridium spp. bacteria?

it is a genus of pathogens which produce potent toxins essential for virulence. They are gram positive spore forms that is commonly found in soil, water, wild animals

What strains are included in the Clostridium spp. ?

-C. tetani


-C. botulinum


-C. perfringens


-C. difficile

What causes botulism?

C. botulinum causes botulism. It is a soil organism which can cause fatal/severe food poisoning.


Its spores find way on food which is improperly processed


Infant and wound botulism is possible

What are some features of C. tetani infections?

it causes tetanus and is found in the soil. Its main RoE is through deep wounds as anaerobic conditions inside lead to spore germination.

Name two neuropathogens ?

C. tetani and C. botulinum cause rapid neurodegenerative diseases. Both pathogens depend on the production of their toxins which are zinc dependent endopeptidases that degrade the extracellular matrix.

What are some clincal symptoms of botulism?

symptoms come on in 8hours-8days


-Vomiting, constipation, urine retention, Double vision, dry mouth and eventually respiratory adn cardiac failure .

how long can it take to recover from botulism?

Took up to 8 months to recover

How does botulinum toxin work?

Axons must take up the toxin by attachment of the heavy chain of the toxin to its surface. The axon then endocytoses the toxin and releases the light chain. this ZMP light chain cleaves SNAP25 which is invovled in vesicle fusion. This prevents the release of acetylcholine from the neuron, preventing neurotransmission. This prevents muscle stimulation.

How does C. tetani toxin work?

It is transported to the spinal cord via retrograde axonal transport and binds to gangliosides at interneuron termini. Here it prevents gylcine release from inhibitory neurones, causing uncontrolled and constant muscle contractions. You get lockjaw, trismus and die from respiratory failure.

Hwo can tetanus be treated?

tetanus is a fairly common infection but can be prevented by treatment with inactive toxins (vaccine). The C terminal cell binding fragment of toxin is used as the toxin.

What conditions can botulism toxic be used therapeutically as a form of treatment?

-Dystonia


-psoriasis


-MS pain


-Bladder control

Where do the majority of bacterial infections take action?

in the intestines, causing food poisoning, water contamination, diarrhoea and vomiting. There is a large number of intestinal pathogens, larger number of disease mechanisms.

What is an enterotoxin?

A protein exotoxin that targets the intestines

Name some bacterias which produce shiga toxins?

-Shigella dysenteria


-E. Coli O104:H4


-Shogatoxigenic E. Coli


- enterohemorrhagic E. coli (EHEC)

What is a distinctive feature of EHEC?

-Most strains are unable to ferment sorbitol and os appear clear not red in sorbitol agar


-It survives acid, heat, osmotic stresses better than other enterobacteriacecae


-it has a very low infectious dose

What are the symptoms of EHEC poisoning?

-begins with watery diarrhoea (1-2 days)


-Blood is then in diarrhoea and severe abdominal pain 4-10 days


-there is no fever or leukocytes in stool


-Haemolytic uraemic syndrome

what two main types of shiga toxin are there?

STX1 and STX2. A bacteria can produce 1 or both . They are also members of the hexameric 1 A and 5 B sububnit toxin family

Where do shiga toxins bind on the host cells?

-They bind to Gb3 (globotriaosylceramide) receptors on host cells



Hwo are shiga toxins activated?

Shiga toxins inhibit protein synthesis by entering a cell via a macropinosome then functioning as a N-glycosidase, cleaving an adenine nucleobase from the 3 region of the 28S RNA of the 60S ribosome in the endoplasmic reticulum

What are the targets for Stx in humans?

GB3 is the main target and can be found in kidney epi adn endothelium, endothelial cells in intestinal, platelets, germinal centre B lymphocytes, Endothelial and dorsal root ganglion cells in the PNS and Neurons in the CNS.

What are the prerequisites for Stx activity

detergent-resistant membranes are needed for Stx activity. These are abundant in the glomerular tissues of kidney.


Stx activates a variety of cell signalling pathways that facilitate its uptake.

What are the clinical features of cholera infection?

-loss of fluid (~20L/day) through diahorrea, causes severe dehydration , renal failure and circulatory collapse.

how can cholera be treated?

rehydration satchets, glucose supplementation and water

Which bacteria produce the Ab5 enterotoxins?

V. Cholerae, Enterotoxigenic E coli , Shigella dysenteriae

how do AB5 enterotoxins cause diahorrea and intestinal damage?

Activates adenylate cyclase in some way, causing a rise in cyclicAMP. This deregulates Na/Cl antiporter channels , causing smassive losses of sodium and chlorine ions. this then causes a net fluid loss to the intestine as water attempts to balance the concentration gradient
-CtxAB genes encoded by bacteriophage