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Penicillin
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Penicillin

Penicillin is an antibiotic produced by the Penicillium notatum mold. The antibiotic effect was originally discovered by a young French medical student Ernest Duchesne studying Penicillium glaucum in 1896 but his work was forgotten. It was later rediscovered in 1928 by Alexander Fleming who noticed that a halo of inhibition of bacterial growth in a culture of Staphylococcus around a contaminant blue-green mould. From the culture plate, Fleming concluded that the mould was releasing a substance that was inhibiting bacterial growth. He grew a pure culture and discovered that the fungus was Penicillium notatum - he later named the bacterial inhibiting substance penicillin after the Penicillum notatum that released it. Unfortunately, Fleming was convinced after conducting some more experiments that penicillin could not last long enough in the human body to kill pathogenic bacteria and stopped studying penicillin after 1931. It would prove to be the discovery that changed modern medicine.

Its chemical structure was determined by Dorothy Crowfoot Hodgkin, enabling synthetic production. A team of Oxford research scientists led by Australian Howard Walter Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass producing the drug. Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work Penicillin has since become the most widely used antibiotic to date and is still used for many Gram-positive bacterial infections.

Penicillin and penicillin derivatives work by inhibiting the formation of peptidoglycan cross links in the bacterial cell wall by directly competing for the reaction site (the beta-lactam ring of penicillin is a chemical analogue for the enzyme that links the peptidoglycan molecules in bacteria) and thus preventing the bacteria from multiplying (or rather causing cell lysis or death when the bacteria tries to divide). See optical isomerism.

Antibiotic resistance to penicillin is now common amongst many hospital acquired bacteria. The resistance to penicillin has been partly (maybe mostly) due to the rise of beta-lactamase producing bacteria which secrete an enzyme that breaks down the beta-lactam ring of penicillin, rendering it harmless to the bacteria.

Penicillin has a molecular formula R-C9H11N2O4S, where R is a variable side chain. It usually comes in two forms: Benzylpenicillin or penicillin G, which must be injected, and phenoxymethylpenicillin or penicillin V which is acid-stable and can be given in tablet form. Although this meant that penicillin could be prescribed in the community for the treatment of infections, the somewhat narrow spectrum of activity of penicillin V led to the search for derivatives of penicillin which could treat a wider range of infections. The first real step forward was in the form of ampicillin. Ampicillin offered a broader spectrum of activity than either of the original penicillins and allowed doctors to treat a huge range of both Gram-positive and Gram-negative infections with one relatively cheap drug. Further development gave us flucloxacillin, important even now for its resistance to beta-lactamases produced by bacteria such as Staphylococcus species. It is still no match for MRSA (Methicillin Resistant Staphylococcus aureus), which was named after flucloxacillin's relative, methicillin.

The last in the line of true penicillins were the antipseudomonal penicillins, such as ticarcillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the beta-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most importantly, the cephalosporins, have it at the centre of their structures.