Natural penicillins or PCNs are penicillin antibiotics that were originally used to treat various bacterial infections following the discovery and purification of penicillin from the mould Penicillinum notatum in the first half of the 20th century. They are derived from mould fermentation and are based on the original penicillin structure as opposed to semisynthetic penicillins which have been modified to have different properties and characteristics. Penicillin G, also known as Benzylpenicillin is the only natural penicillin still in use.
One of the most important and most widely used medications to this day, penicillin was discovered by the Scottish bacteriologist Sir Alexander Fleming in 1928. The Nobel laureate, however, discovered the “miracle” compound by an accident. He was studying the bacterium Staphylococcus aureus when one of the samples was accidentally contaminated by the mould Penicillinum notatum.
Fleming noticed that the substance produced by mould - penicillin - killed the bacteria which encouraged him to start researching its anti-bacterial properties. He found it to be effective against a wide range of Gram-positive and some Gram-negative bacteria but he wasn’t able to produce penicillin in sufficient quantities to be able to test it as medication for humans. This was possible only in the early 1940s when Howard Florey and Ernst Boris Chain succeeded in what Fleming repeatedly failed. They managed to produce penicillin in quantities large enough to test its efficacy in humans and launch its mass production before the end of the Second World War.
No matter if being natural or semisynthetic, all penicillins kill bacteria by inhibiting cell wall production, more specifically by destroying enzymes that produce bacterial cell wall, and stimulating activation of enzymes that shatter the bacterium’s protective wall. In comparison to semisynthetic penicillins, however, the only natural penicillin still in use is very unstable in acidic environment. In order for it to work, it must be given in the form of injection. Semisynthetic penicillins, on the other hand, are much more stable in acid and are appropriate for oral administration as well.
Another thing that limits the use of natural penicillins is the fact that many strains of bacteria that were previously susceptible to the drug have developed resistance to it. To overcome this issue, the so-called penicillinase-resistant penicillins such as methicillin were developed but unfortunately, there are now also strains that are resistant to these types of penicillin as well. One of the best examples is methicillin-resistant Staphylococcus aureus (MRSA) which is sensitive only to a handful antibiotics.