Development of Antibiotics: Part 1 Flashcards
What are Sulphonamides and how do they work?
Sulphonamides are antibiotics. They fight against streptococcal infections. They stop the production of gram positive bacteria It acts as a precursor to folate biothynthesis. It stops bacterial growth.
What diseases do streptococcus species cause?
scarlett fever. Septicaemia. Pneumonia. Meningistis
Who discovered sulphonamides and what was his research on?
Gerard Domagk. He worked on azo dyes. He found out that injecting them into white mice, they were converted into sulphonamides.
Describe the discovery of Penicillin. Touch on who discovered it, what the discovery showed.
Alexander Fleming discovered penicillin in 1928. Mould growing on petri dishes and created zones of inhibition. This showed penicillin mould can kill bacteria.
What exactly is penicillin?
Beta lactum ring, earliest form of penicillin
Who tried to purify penicillin and failed?
Professor Harold Raistrick at the London school of hygiene and tropical medicine.
Who discovered penicillins therapeutic properties and purified it?
Ernst Chain and Howard Florey in 1939, at Uni of Oxford, developed Fleming’s work. They were able to purify it and use it on a patient. They ran out and he died, but proved it worked as it kept him alive.
Describe how penicillin was engineered in the 1940s.
sealed off (using cotton wool) glass vessel. media inside, penicillium mould produced on the surface of the liquid, penicillin excreted into the media. Penicillium grew at the interface of the liquid-air boundary. you would pour off the liquid, get rid of the biomass (mould) and go about purifying antibiotic from the liquid.
What did the media inside the sealed glass vessel, that enabled penicillium growth, consist of?
Glucose, general vitamins and minerals that came from yeast extract
How was the glass vessel idea ‘scaled up’?
Using modified bedpans. It was a linear scale up. they would sterilise it, add the culture and let the mould grow for about a week then harvest the antibiotic.
Was the scale up a good idea or not? Explain
It wasn’t a clever idea. due to WWII, it was made difficult for Florey and chain to industrialise penicillin. The media used (glucose) was not effective in producing antibiotics.
What was the engineering challenge of the 1940s?
The media needed to be optimised for maximum penicillin growth and reactors needed to be designed.
Where did Florey fly to, in order to get help industrialising penicillin?
Flew to America and visited USDA northern regional research lab as they had huge pharmaceutical companies and they were not getting bombed at the time.
Who had reactors that could mass produce penicillin? Why? What type of system did they have?
Pfizer as they already had experience in liquid fermentation processes as they manufactured the citric acid for coca cola and other beverages. They had an aerated liquid fermentation system. Microbes need air.
Who developed the liquid culture of Penicillium and how?
Andrew Moyer’s group at USDA. They improved the yields of penicillin tenfold using ‘shake-flasks’. They optimised the growth media for optimum penicillin production.
What are shake flasks?
used to optimise the penicillium media. use a heated rod. if you shake the flask on an orbital shaker, the baffles break up the liquid flow, provides good aeration.
What did Andrew Moyer’s group discover what wasn’t good for the liquid culture?
That glucose is not a good source of carbon for the development of antibiotics. That lactose produced a lot more antibiotics. The actual fungus grows great with glucose, but not the antibiotic.
What carbon and nitrogen source did Andrew Moyer’s group discover was good for the liquid culture?
Corn steep liqueur increased yields many many folds. it was effective to use as it is a waste product from starch manufacture. For a nitrogen source, sodium nitrate. calcium carbonate and phenylacetate were also used to increase the yield of benzylpenicillin.
who designed the first commercial penicillin production plant for Pfizer?
Margaret Hutchinson Rousseau. American chemical engineer. one of the women who played an active role in the mass development of penicillin. 1st women to join the institute of chemical engineers.
What was the main advantage of developing penicillin during the 1940s?
WW11. Patients could get treated.
