BIOL243 - L20 - Bacterial pathogens - merging threats and alternative therapies

  • Created by: Katherine
  • Created on: 30-04-17 12:13
What are the pathogens of the microbial world?
Viruses, bacteria, fungi, algae and proozoa
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How many bacterial cells are on the Earth?
5x 10^30
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How many viruses are there?
10-100:1 (viruses outnumber bacteria)
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What is the total amount of bacterial carbon in the soil?
5 x 10^17 (weight of the UK)
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Where are pathogens found?
In every group (e.g. virus, bacteria, fungi, protozoa and algae)
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What is Yesinia pestis?
It is the bacteria which causes the plague
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Where is Yersinia Pestis found?
In wild rodents
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What is our main threat of the plague?
Bioterrorism
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What else are emerging threats?
Legionellosis, Camplyobacter jejuni
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What are the threats assocaited with refridgeration?
Risk factor for disease/ contamination of interior surfaces . You can also get cross contamination to other food items, including higher risk ready to eat foods
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How do chickens get campylobacter jujuni?
Because they're stressed and kept in poor conditions,they have poor immune systems, making them predisposed to campylobacter.
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What is a biofilm?
A range of bacteria which will colonise a surface and cause a major problem.
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Where are biofilms common?
Catheters (contamination), implant (contamination), gum disease.
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Biofilms don't always have to be localised, they can be
septicaemic
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Why is it an issue to have iofilms?
We cannot treat them = antibiotics ineffiecient
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What are a key facctor of resistance moement?
Airlines and travel
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If antibiotics are becoming less effective, what do we do?
Use less antibiotics (be selevtice, don't give them lightly) Develop new antibiotics or combinations , use poo
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How can you improve antibiotics?
Combine them with other antibiotics and combine them with protection.
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Give an example of an antibiotic combined with other antibiotcs?
Multiple resistant Tb, Isoniazid and rifampicin for 6 months. Combined with pyrazinamide and ethambutol for first 2 months of the 6 month treatment period.
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Give an example of an antibiotic combined with protection?
Augmentin (amoxicillin and the B lactamse inhibitor, potassium clavulanate), inhibitor protects the B lactam of amoxicillin from B lactamase, resistance needs to inhibit both B lactam and potassium clavualanate. Resistance to amoxicillin>augmentin
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What is a bacteriophage?
A virus that infects bacteria
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Phages are.. and can be found where?
Ubiquitous and can be found in all reservoirs populated by bacterial hosts, from soils to the intestines of animals
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Where are many bacteriophage found?
Sea water - it is a dense natural source for phages and other viruses (9x10^8 virions ml-1)
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What percentage of marine bacteria may be infected by phages
70%
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How big are bacteriophages?
Smaller than the bacteria they destroy
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What is the structure of a phage?
They have a head (capsid) and a tail. They have a collar and a core area. They have a helical sheath and tail spikes. They contain ssRNA, dsRNA, ssDNA or dsDNA (circlular or lnear)
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How to temperae phages attack?
Either and lysogenic pathway or lytic.
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What is the lytic cycle?
The phage attaches to host cell and injects DNA, phage circularizes new phage DNA and proteins are synthesized and assembled into prophages. Thr cell lyses, releasing phages
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What is the lysogenic cycle?
The phage attaches to host cell and injects DNA, phage circularizes, phage DNA integrates into the bacterial chromosome, becoming a prophage, the bacterium reproduces normally, copying the prophage and transmitting it to daughter cell. Many c
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Which type of phage is more effective?
Lytic
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What are the potential applications for bacteriophages?
For food safety, as biomarkers of health/disease, as reporters of microbiome diversity, as delivery vectors, a drivers of microbiota, for disease therapy
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What is phage therapy?
PT is therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections
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What is PT used for?
To treat bacterial infections in Easten Europe over 80 years
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Will Phages replace antibiotics as the first line?
No - however promising role for phages in situations where antibiotics alone are not sufficient
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What is the source and propagtion of bacteriophage?
Isolation involves collecting local samples of water. Likely to contain high quantities of bacteria and therefore, bacteriophages. (e.g. effluent outlets, sewage). And also corpses
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How do you grow bacteriophages?
Go to a sewage plant, collect the water and spread on to target pathogen
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Once you have grown the bacteriophages on the target pathogen, what do you do?
You centrfuge the infected bacterial culture with extracellular phage and are left with a pellet of bacteria and a phage suspension
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What happens the phage suspension?
The lytic phage are amplificed on cultures of the target bacteria, passed through a filter to remove all but the phages.
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What are the advantages of phage therapy over antibiotics?
Can be very effective, when super bacterium appears, the superphage already attacks it (isolate from the same environment). They have localized use. They stop reproducing once target bacteria is destroyed.
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As with antibiotics, bacteria can become resistant to treatmetns through mutation. How do phages get around this?
However, evolution drives the rapid emergence of new phages that can destroy bacteria that have become resistant. This means that there should be an 'inexhaustible' supply
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What are the disadvantages of PT over antibiotics? 1
Unlike some antibiotics, phage must be refrigereated. Doctors need special training to use this methd. Difficulty treating a multiple infection. Mixtures consisting of several phage can fight mixed infections.
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For the best results, the phage should be:
Tested in the lab prior to application, makes phage less suitable for acutre cases where time is not available
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What are the disadvantages of PT over antibiotics? 2
Intravenous phage application: recognized by the human immune and antibodies are produced The high bacterial strain specificity of phage therapy requires different cocktails for treatment of the same infection (diseases differ region to region).
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What are disadvantage?
Mixture of phage is often applied for efficiency. Requires updated bank of phage. No lytic phage for clostridium difficile, to work the virus has t reach the site of the bacteria and viruses don't always reach the same places that antibiotics do,
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Will the opinion of viruses help in the PT?
The negative public perception of viruses may also play a role in the reluctance to embrace phage therapy
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What are the phage delivery routes?
Parenteral (non-oral), oral or local delivery
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What are the parenteral delivery routes of phage?
Intramuscular (IM), subcutaneous (SC) or intra-peritoneal (IP)
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What are the oral delivery routes of phage?
Gastro-intestinal infections - has to overcome acidic environment - microencapsulation
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What are the local delivery routes of phage?
wound healing - within hydrogel (+ntibiotics). Topical (applied to wounds), Chronic otitis (to treat P.aeruginosa), Dental phage (enterococcus faecalis), inhalation via nebuliser, preventing biofils on medical devices by spraying it with phages
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Phages have been identified as a potential means to eliminate pathogens from::
Raw food (campylobacter) fresh food (listeria) to reduce food spoilage bacteria
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What are the agricultural practice phages (Farms)?
To get rid of campylobacter, escherichia and salmonella on farm animals
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What are the agricultural practice phages (Fish farms)?
Fish from aquaculture lactococcus spp and vibrio spp pathogens
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What are the agricultural practice phages (plats of agricultural importance)
To get rid of Rewinia and Xanthomonas
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What is a natural sourced item with antimicrobial properties?
Manuka honey
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How many microorganisms is manuka honey effective against?
80 microorganisms
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How does Manuka honey act agaisnt microorganisms?
It alters their osmolarity, because honey is very high sugar so it sucks out the water from the cells. It has peroxide activity and so has free radical activity which attack the cells and also methylglyoxal which target membrane proteins = unstable
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Manuka honey decreases...
Quorum sensing (stops them communicating), siderophores (they can't get iron) and surface adhesion
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How does Manuka honey effect biofilms?
It inhibits biofilm formation and disrupts established biofilms
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What does Manuka honey inhibit?
Adhesion to epithelial cells and binding to human cells
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What is the name of the new antibiotic that came out last year?
Teixobactin
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What is Teixobactin active against?
Clostridium difficile, bacillus anthracis, S. Aureus (MRSA) and M.tuberculosis
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What is Teixobactin ineffective against?
Most gram negative bacteria
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What is the positives of the Teixobactin?
It is effective at low dose
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