Nutrition 4: Antibiotic discovery Flashcards
What are the 5 clinically validated targets for antibiotics
Inhibiting
- Bacterial cell wall synthesis,
- Protein synthesis
- RNA/DNA synthesis
- Metabolite synthesis (ie folates)
- Activating Membrane Disruption.
Compare the two types of antibiotics and give examples
Bacteriocidal: kill bacteria - eg Penicillin
Bacteriostatic: inhibit growth - eg Tetracyclines and sulphonamides
Who are the two people that discovered penicillin
1st about 1900 by Ernest Duchesne
2nd 1928 by Alexander Fleming
How did Alexander Fleming discover penicillin
Fungal spore of penicillium from Freeman’s laboratory below got into his plating of bacteria (staph). It inhibited the growth.
Why is penicillin discovery really lucky
- only one penicillum mould in freemans lab
- plating time is very short
- Penicillin only works on young bacteria, so the cold summer let the fungus grew first.
Who is credited with the potential of penicillin as a therapeutic agent
Lord Florey and Ernest Chain.
What experiment proved penicillin worked in the living body
The experiment:
- peritoneal injection of 2 groups with bacteria
- then next day given 8 hourly injections of penicillin to one group.
-Results:
To 36 hours some mice got sick and died but from 36-48 remaining mice survived and were indistinguishable from healthy.
The control group all died
What is the name of penicillium from in latin
“Paintbrush” like spores - penicillus
What were penicillins uses during the WWII and after
During War was wound pathogens like Staphylococcus and after was rheumatic fever and syphillis
What is the difference between gram positive and gram negative bacteria
Both have an inner membrane then peptidoglycan cell wall with periplasm in between but gram negative has an extra outermembrane
Why does inhibiting cell wall synthesis kill bacteria
As the cell is starting to grow it cannot make new cell wall to accomodate the growing cell so as it continues, cytoplasm covered in cell membrane begins to squeeze through gaps in the cell wall. It still can’t make daughter cells because it can’t make any cell wall and then eventually sheds the whole thing completely, making a spheroplast which is extremely vulnerable to cell lysis.
How does penicillin work as an inhibitor of cell wall synthesis
Penicillin covalently binds to the DD transpeptidase enzyme as it is mimetic of DalaDala substrate.
Its a suicide inhibitor that stops this enzyme from performing the last step in cell wall synthesis of forming cross links between peptidoglycan chains
Give example of how antibiotic inhibiting protein synthesis causes bacteria cell death
Aminoglycosides (chloramphenicol, streptomyocin) bind to bacterial ribosomal RNA, disrupt ribosomal structure leading to misfolded proteins destined for cell membrane which can cause cell death
Give example of how antibiotic inhibiting DNA/RNA synthesis causes bacteria cell death
Rifamycin class binds to actively transcribing RNA polymerase, stopping the production of RNA and therefore proteins
Give example of how antibiotic inhibiting metabolite synthesis causes ihibited bacteria growth
Sulfonamides competitively inhibit dihydropteroate synthetase, the enzyme that converts PABA to folic acid, and this stops bacteria from making DNAs
