Researchers from Imperial College London, CABI and the University of Oxford have sequenced the genome of Fleming's original Penicillium strain using samples that were frozen alive more than 50 years ago.
In the year 1928, Alexander Fleming discovered the first antibiotic, penicillin while working at the St. Mary’s Hospital Medical School, now part of Imperial College London. He identified antibiotic properties produced by a mould – which had the genus penicillium – growing in a petri dish. 50 years later, researchers have successfully sequenced the genome of this mould and for the first time compare it with other versions.
The research team compared the genomes of Fleming’s mould with two strains of penicillium from the United States that is used to produce antibiotics at an industrial scale. Results of this study was published in September 2020 in Scientific Reports and demonstrated that both strains adopted slightly different methods in producing penicillin. Potentially suggesting the possibility of new techniques in antibiotic industrial production.
Lead researcher Professor Timothy Barraclough, from the Department of Life Sciences at Imperial and the Department of Zoology at Oxford, said, "We originally set out to use Alexander Fleming's fungus for some different experiments, but we realised, to our surprise, that no-one had sequenced the genome of this original Penicillium, despite its historical significance to the field."
Industrial production of penicillin in the United States uses the fungus from mouldy cantaloupes, which are then artificially selected from specific strains to produce higher volumes of penicillin.
The team re-grew Fleming's original penicillium from a frozen sample kept at the culture collection at CABI and extracted the DNA for sequencing. During the comparison between Fleming’s original sample and the strains from the United States, the researchers paid attention to two types of genes; those encoding the enzymes that the fungus uses to produce penicillin; and those that regulate the enzymes, for example by controlling how many enzymes are made.
In both samples, regulatory gene were found to have the same code, however, the United States sample had more copies of these genes, which could be assisting in the high production of penicillin. Genes that coded for penicillin-producing enzymes were also different between the samples. The team suggested that this demonstrates that wild penicillium in the UK and US evolved naturally to produce slightly different versions of these enzymes.
Microbial evolution remains a challenge today with the increasing resistance to antibiotics. The researchers are still unable to confirm the consequences of the difference in enzyme sequences between the two samples.
First author Ayush Pathak, from the Department of Life Sciences at Imperial, said: "Our research could help inspire novel solutions to combatting antibiotic resistance. 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."