Discovery

This is one of the first and still one of the most widely used antibiotic agents, derived from the Penicillium mold. Sir Alexander Fleming in 1928 first observed that colonies of Staphylococcus Aureus, a pus producing bacterium, failed to grow in those areas of a culture that had been accidentally contaminated by the green mold, Penicillium Notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substnce capable of killing many of the common bacteria that infect humans. Other researchers created an injectable agent for therapuetic use in 1940.

The several kinds ofpenicillin synthesized by various species of the mold Penicillium may be divided into two classes: Biosynthetic penicillins (those formed during the process of mold fermentation) and semisynthetic penicillins (those in which the structure of a chemical substance, 6 aminopenicillanic acid, found in all penicillins is altered in various ways). Because it is possible to change the characteristics of the antibiotic, different types of penicillin are produced for different therapuetic purposes.

Benzylpenicillin, or penicillin G, is the only naturally occuring penicillin that is still used clinically. Because of its poor stability in acid, much of penicillin G is broken down as it passes through the stomach, as a result of this characteristic, it must be given by intramuscular injection, which limits its usefulness. Some of the semisynthetic penicillins are more acid-stable and so may be given as oral medicine.

All penicillins work in the same way, namely, by inhibiting the bacterial enzymes responsible for cell-wall synthesis and activating other enzymes to break down the organisms' protective walls, therefore, they are not effective against microorganisms that do not produce cell walls.

Some strains of previously susceptible bacteria have developed a specific resistance to penicillin, these bacteria either produce penicillinases, (enzymes that disrupt the internal structure of penicillin and thus destroy the antimicrobal action of the drug), or they lack cell-wall receptors for the penicillin, greatly reducing the drug's abilty to enter bacterial cells.

Among the bacteria sensitive to penicillin are those that cause throat infections, pneumonia, spinal meningitis, gas, gangrene, diptheria, syphilis and gonorrhea. The main side effects of penicillin are allergic or hypersensitivity reactions including skin rashes, hives, swelling, and anaphylaxis, or allergic shock.

Penicillin
The Reconquista

Important Dates

Year Place Description
Ancient Times Greece and China The ancient Greeks and ancient Chinese, already used moulds and other plants to treat infection.
1640 England The idea of using mould as a form of treatment was recorded by apothecaries, such as John Parkington, King's Herbarian, who advocated the use of mould in his 1640 book on pharmacology.
1870 England Sir John Scott Burdon-Sanderson, who started out at St. Mary's Hospital 1852–1858 and as a lecturer there 1854–1862 observed in 1870 that culture fluid covered with mould would produce no bacteria.
1871 England Joseph Lister, an English surgeon, was prompted by Burdon-Sandersons discovery to investigate and describes in 1871 that urine samples contaminated with mould did not allow the growth of bacteria and he also described the antibacterial action on human tissue on what he called Penicillium Glaucum. A nurse at King's College Hospital, whose wounds did not respond to any antiseptic, was then given another substance which cured her, and Lister's registrar informed her that it was called Penicillium.
1874 England William Roberts observed in 1874 that bacterial contamination is generally absent in cultures of the mould Penicillium glaucum.
1875 England John Tyndall followed up on Burdon-Sanderson's work and demonstrated to the Royal Society the antibacterial action of the penicillium fungus in 1875.
1877 France Louis Pasteur and Jules Francois Joubert in 1877 had observed that cultures of the anthrax bacilli, when contaminated with moulds, became inhibited. Some references say that Pasteur identified the strain as Penicillium notatum.
1897 France Ernest Duchesne at École du Service de Santé Militaire in Lyons then independently discovered healing properties of a penicillium glaucum mould, even curing infected guinea pigs from typhoid and published a dissertation in 1897 but this was ignored by the Institut Pasteur. However Duchesne was himself using a discovery made by Arab stable boys, who were using moulds to cure sores on horses. He did not claim that the mould contained any antibacterial substance, but simply claimed that the mould somehow protected the animals.

Duchesne cured typhoid, but the penicillin isolated by Fleming does not cure typhoid.

Duchesne injected a mould with the fungus penicillium glaucum. In contrast, Fleming isolated the substance penicillin from a mould containing penicillium notatum.

The term penicillium glaucum was used as a catch-all phrase at the time for different fungi, but not for penicillium notatum and the mould was unfortunately not preserved, which makes it impossible to be certain today which fungus might have been responsible for the cure, and consequently even less certain which substance was responsible.
1920 Belgium In the 1920's, Andre Gratia and Sara Dath observed a fungal contamination in one of their Staphylococcus aureus cultures that was inhibiting the growth of the bacterium. They identified this as a species of Penicillium and presented their observations as a paper. There was little attention to this paper.
1929 UK Fleming noticed a halo of inhibition of bacterial growth around a contaminant blue-green mould on a Staphylococcus plate culture. He concluded that the mould was releasing a substance that was inhibiting bacterial growth. He grew a pure culture of the mould and discovered that it was Penicillium notatum. With help from a chemist he isolated what he later named "penicillin". During the next twelve years, he grew and distributed the original mould, unsuccessfully trying to get help from any chemist that had enough skill to make a stable form of it for mass production.
1938 UK In Oxford, Howard Walter Florey organized his large and very skilled biochemical research team, notable among them Ernst Boris Chain and Norman Heatley, to undertake the innovative work to produce a stable penicillin.

 

alexander fleming
Alexander Fleming