How do antibiotics work
Penicillin discovery
Active ingredient:
Penicillin
Natural product:
Penicillin
Derived from:
Penicillium notatum mould
Alexander Fleming is recognised as the person who discovered the first antibiotic in 1928. However, the ancient Egyptians were known to treat infected wounds with mouldy bread - this is probably the first known use of penicillin.
Fleming was studying colonies of bacteria on petri dishes when he noticed something unusual on one dish. He noticed that there was a strange colony of mould on one dish, and the area around it was clear from bacteria.
Fleming investigated further, and found that the 'mould juice' was able to kill a wide range of bacteria. His assistants then worked to isolate the penicillin from the mould juice. This pure isolate wasn't very stable or effective, but they published their results in the British Journal of Experimental Pathology in 1929.
In 1939, Howard Florey and his team were working at Oxford University on the purification and chemistry of penicillin. They conducted animal experiments and produced the mould filtrate in large batches.
Over the next ten years, the processes were refined and in 1941, the first human patient was treated successfully with penicillin.
Pharmaceutical companies such as Glaxo (GlaxoSmithKline) and Kemball Bishop (now Pfizer) took over the industrial production of penicillin.
Penicillins - refinement
Different types of penicillins are synthesised to change their activity profile.
Can you guess the structure of penicillin's pharmacophore from looking at the structures below?
penicllin V
penicillin G
Amoxicillin
Ampicillin
Cloxacillin
oxacillin
How do antibiotics work?
Antibiotics are medicines that fight bacterial infections.
In order to treat infections from bacteria, we need to understand how they work, and what their weak points are. There are many different ways to combat bacterial diseases. For example, if we can design molecules that break down the cell walls of bacteria, those bacteria will die. But this mechanism won't work for bacteria that don't have cell walls.
Some methods are more effective than others, but scientists also have to weigh up the side effects. Is the treatment good enough to justify negative side effects?
Unfortunately, just because a medicine once worked to combat a pathogen, doesn't mean it always will. You may have heard the term resistance in the news.
As pathogens are also living things, they can evolve to reduce their vulnerability to certain medicines. Scientists are concerned that many antibiotics will not be useful for much longer, which means that it is really important for us to keep developing new medicines. But who is going to fund this expensive research, particularly when we have a large range of antibiotics available right now?
The E$$ENTIAL MEDICINE$ project is hoping we might inspire you to become involved in solving this problem with us.
Bacteria
Bacteria are microscopic, single-celled organisms. They are prokaryotic.
Recall that bacteria have genetic material (DNA) inside the cytoplasm of the cell. Many have cell walls or capsules that protect them from harsh environments like stomach acid. Ribosomes read DNA and use this to make proteins. Proteins are used in growth and replication.
Some bacteria are helpful, and others cause disease.
Bacteria replicate using the process of binary fission.
Examples:
Yersinia pestis - causes Black Plague
Escherichia coli - diarrhoea
Mycobacterium tuberculosis - tuberculosis
Benzylpenicillin
Pencillins work by preventing the bacteria from synthesising a molecule called peptidoglycan. This molecule is a key building block in the cell wall of the bacteria, which provides the wall with the strength it needs to survive within the human body. Without a fully functioning cell wall, the bacteria cells die and the patient can recover.
ESSENTIAL
doxycycline
Doxycycline is a tetracycline antibiotic which prevents bacterial growth by binding to the ribosome and preventing the ribosome from functioning. The ribosome is an important organelle for the bacteria, because it controls protein synthesis. Without protein synthesis, the bacterial cells cannot produce essential proteins or reproduce. It eventually dies, and the patient can recover.
ESSENTIAL
Delafloxacin
Delafloxacin is a fourth generation fluoroquinolone which prevents bacteria from replicating by inhibing the activity of key proteins involved in bacterial cell replication. If bacterial cells cannot replicate, no new bacterial cells are made to replace those that die naturally. The bacterial infection of the patient subsides and the patient can recover.
NON-ESSENTIAL