Penicillin: fungus accidentally grown by Fleming in 1928 has its genome sequenced for the first time – Daily Mail

The penicillin mould accidentally grown by physician and microbiologist Alexander Fleming in London in 1928 has had its genome sequenced for the first time.

Researchers from the UK used frozen samples of Sir Fleming’s original strain of the fungus — and compared them with their modern, industrially-used counterparts.

The sample of Sir Fleming’s strain they grew had been kept ‘on ice’ in the culture collections at the Centre for Agriculture and Bioscience International, Oxfordshire. 

They found that the wild UK strain used a slightly different method to produce penicillin than the strains current used to manufacture the antibiotic in the US.

The findings could suggest new routes to improve the widescale production of the drug, which is used to treat a variety of bacterially derived infections. 

The penicillin mould accidentally grown by physician and microbiologist Alexander Fleming in London in 1928 has had its genome sequenced for the first time. Pictured, a sample of mould regrown from one of Sir Fleming's frozen samples

The penicillin mould accidentally grown by physician and microbiologist Alexander Fleming in London in 1928 has had its genome sequenced for the first time. Pictured, a sample of mould regrown from one of Sir Fleming's frozen samples

The penicillin mould accidentally grown by physician and microbiologist Alexander Fleming in London in 1928 has had its genome sequenced for the first time. Pictured, a sample of mould regrown from one of Sir Fleming’s frozen samples

Alexander Fleming, pictured, discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London

Alexander Fleming, pictured, discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London

Alexander Fleming, pictured, discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London

Sir Fleming discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London.

He noticed that, in the dish — which had been left exposed near an open window, where it became contaminated by the mould — the Staphylococcus bacteria he had left cultivating during a vacation to Suffolk had died where the fungus had grown.

In contrast, Staphylococci colonies growing further away from the mould were untouched — an observation that led him to remark ‘That’s funny.’

Sir Fleming was awarded the 1945 Nobel Prize in Physiology or Medicine for his work on penicillin and antibiotics, along with colleagues Ernst Chain and Howard Florey.

Although Sir Fleming’s strain of the mould is famously referred to as the ‘original source’ of penicillin, production of the antibiotic in the US quickly switched over to using a different type — one that grew on mouldy cantaloupes.

Furthermore, this naturally-derived fungus went on to change over time, as drug manufacturers artificially selected for strains that produce higher volumes of penicillin and therefore proved to be more lucrative to use.

In their study, the researchers grew mould from an original sample of Sir Fleming’s fungus that had been kept frozen in the culture collections of the Centre for Agriculture and Bioscience International.

‘We originally set out to use Alexander Fleming’s fungus for some different experiments,’ said paper author and evolutionary biologist Timothy Barraclough of Imperial College London and the University of Oxford.

‘But we realised, to our surprise, that no-one had sequenced the genome of this original Penicillium, despite its historical significance to the field.’

Researchers from the UK analysed frozen samples of Alexander Fleming's original strain of the fungus — and compared them with their modern, industrially-used counterparts. Pictured, a sample of mould cultivated from one of Sir Fleming's frozen samples

Researchers from the UK analysed frozen samples of Alexander Fleming's original strain of the fungus — and compared them with their modern, industrially-used counterparts. Pictured, a sample of mould cultivated from one of Sir Fleming's frozen samples

Researchers from the UK analysed frozen samples of Alexander Fleming’s original strain of the fungus — and compared them with their modern, industrially-used counterparts. Pictured, a sample of mould cultivated from one of Sir Fleming’s frozen samples

Professor Barraclough and colleagues focussed in particular on two kinds of genes — those that encode for the enzymes that the fungus uses to produce penicillin, and those that regulate these enzymes, for example by controlling their manufacture.

The team found that both Sir Fleming’s UK strain and those used industrially in the US had the same regulatory gene code — but the latter variants of the fungus had more copies of the regulatory genes, allowing them to make more of the drug.

Furthermore, the researchers discovered that the genes that code for the penicillin-producing enzymes were different between the strains isolated in the UK and the US.

This, they said, reveals that wild Penicillium evolved differently between the two countries, leading to slightly different versions of the enzymes. 

As moulds like Penicillium produce antibiotics to help them fight off microbes, it is likely that the UK and US strains differ because they had adapted to best combat the local bacterial populations that each strain faced.

They found that the wild UK strain used a slightly different method to produce penicillin than the strains current used to manufacture the antibiotic industrially. Pictured, a sample of Sir Alexander Fleming's original strain of Penicillium, which was preserved frozen in a glass tube

They found that the wild UK strain used a slightly different method to produce penicillin than the strains current used to manufacture the antibiotic industrially. Pictured, a sample of Sir Alexander Fleming's original strain of Penicillium, which was preserved frozen in a glass tube

They found that the wild UK strain used a slightly different method to produce penicillin than the strains current used to manufacture the antibiotic industrially. Pictured, a sample of Sir Alexander Fleming’s original strain of Penicillium, which was preserved frozen in a glass tube

‘Our research could help inspire novel solutions to combatting antibiotic resistance,’ said paper author and biologist Ayush Pathak, also of Imperial College London.

‘Industrial production of penicillin concentrated on the amount produced and the steps used to artificially improve production led to changes in numbers of genes.’

‘But it is possible that industrial methods might have missed some solutions for optimising penicillin design — and we can learn from natural responses to the evolution of antibiotic resistance.’

The full findings of the study were published in the journal Scientific Reports.

Sir Fleming discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London. Pictured, the frozen fungal sample

Sir Fleming discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London. Pictured, the frozen fungal sample

Sir Fleming discovered the first-known antibiotic when a mould of the genus Penicillium accidentally started growing in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London. Pictured, the frozen fungal sample

The findings could suggest new routes to improve the industrial production of the drug, which is used to treat a variety of bacterially derived infections. Pictured, vintage Penicillin products manufactured in the mid-century by Glaxo

The findings could suggest new routes to improve the industrial production of the drug, which is used to treat a variety of bacterially derived infections. Pictured, vintage Penicillin products manufactured in the mid-century by Glaxo

The findings could suggest new routes to improve the industrial production of the drug, which is used to treat a variety of bacterially derived infections. Pictured, vintage Penicillin products manufactured in the mid-century by Glaxo

THE IMPACT OF SIR ALEXANDER FLEMING’S WORK ON PENICILLIN

Pictured: Sir Alexander Fleming, who discovered penicillin in 1928

Pictured: Sir Alexander Fleming, who discovered penicillin in 1928

Pictured: Sir Alexander Fleming, who discovered penicillin in 1928

Sir Alexander Fleming was born at Lochfield near Darvel in Ayrshire, Scotland on August 6th, 1881. 

He spent four years in a shipping office before entering St. Mary’s Medical School, London University. He qualified with distinction in 1906 and began research at St. Mary’s under Sir Almroth Wright, a pioneer in vaccine therapy. 

He served throughout World War I as a captain in the Army Medical Corps, being mentioned in dispatches, and in 1918 he returned to St. Mary’s. 

He was elected Professor of the School in 1928 and Emeritus Professor of Bacteriology, University of London in 1948. He was elected Fellow of the Royal Society in 1943 and knighted in 1944.

Sir Alexander wrote numerous papers on bacteriology, immunology and chemotherapy, including original descriptions of lysozyme and penicillin.

Dr Fleming died on March 11th in 1955 and is buried in St. Paul’s Cathedral. 

Sir Fleming is best-known for his serendipitous discovery of the first antibiotic, penicillin, in a Petri dish in his laboratory at the St Mary’s Hospital Medical School, which is today part of Imperial College London.

He noticed that, in the dish — which had been left exposed near an open window, where it became contaminated by the mould — the Staphylococcus bacteria he had left cultivating during a vacation to Suffolk had died where the fungus had grown.

In contrast, Staphylococci colonies growing further away from the mould were untouched — an observation that led him to remark ‘That’s funny.’

Sir Fleming was awarded the 1945 Nobel Prize in Physiology or Medicine for his work on penicillin and antibiotics, along with colleagues Ernst Chain and Howard Florey.

Penicillin revolutionised medicine, providing as it did the first-ever drug that could be used to treat bacterial infections and fight conditions that before would likely have proven fatal — like septicaemia, or blood poisoning.