Genome of Alexander Fleming's original penicillin mould sequenced
The research may help in the fight against antibiotic resistance, scientists from Imperial College say.
Alexander Fleming famously discovered penicillin in one of science’s greatest good luck stories in 1928 while working at St Mary's Hospital Medical School. It was produced by a mould in the genus Penicillium that accidentally started growing in a Petri dish he was using to study the bacteria staphylococcus aureus. Much to his surprise he noticed that the mould was suppressing the growth of the bacteria and so the first antibiotic was discovered.
Now, researchers from Imperial College London, the Centre for Agriculture and Bioscience International (CABI) and the University of Oxford have sequenced the genome of Fleming's original Penicillium strain by re-growing it from a frozen sample kept at the culture collection at CABI.
“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,” said lead researcher Prof Timothy Barraclough, from the Department of Life Sciences at Imperial and the Department of Zoology at Oxford.
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Although Fleming's mould is famous as the original source of penicillin, industrial production quickly moved to using fungus from mouldy cantaloupes in the US, in which the Penicillium samples were artificially selected for strains that produce higher volumes of penicillin.
By comparing the genomes of Fleming’s strain to two strains currently used in the US, they found several key differences in the genes that code for penicillin-producing enzymes found in the different funguses. The researchers say this shows that wild Penicillium in the UK and US evolved naturally to produce slightly different versions of these enzymes and could potentially be of aid in the fight against antibiotic resistance.
“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,” said first author Ayush Pathak, from the Department of Life Sciences at Imperial. “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.”
Reader Q&A: How do antibiotics work?
Asked by: Katrine Mellersh, Durham
Lots of chemicals kill bacteria (bacteriocidal compounds), or slow down their replication (bacteriostatic compounds), for example bleach or cyanide. The trick is finding those that don’t do the same to humans. These ‘antibiotics’ can work in many ways: they simply need to disrupt something specific to bacterial biochemistry.
One easily reached feature is the mesh surrounding the bacterium: the cell wall. It’s made by linking together simple sugars and short amino acid chains. Many classes of antibiotics (including cephalosporins and penicillins) work because they strongly bind onto (so clog up) the bacterial machinery that links the chain-ends together. Alternatively, vancomycin binds to the amino acid chain-ends themselves, while bacitracin prevents the bacteria from moving its cell wall chemicals to the outside.
Another major target is the ribosome, that intricate combination of molecules that assembles proteins (the cell’s working machines) from DNA. Bacterial and non-bacterial ribosomes differ quite a lot in molecular structure. Antibiotic drugs like tetracycline, erythromycin, streptomycin and neomycin bind to bacterial ribosomes, clogging them up so that proteins can’t be made. The bacterium eventually stops functioning. Many other antibiotic mechanisms exist. For example, quinolones block the bacterial DNA untangling machinery, while sulfonamides block folate production (needed for making DNA).
Jason is the commissioning editor for BBC Science Focus. He holds an MSc in physics and was named Section Editor of the Year by the British Society of Magazine Editors in 2019. He has been reporting on science and technology for more than a decade. During this time, he's walked the tunnels of the Large Hadron Collider, watched Stephen Hawking deliver his Reith Lecture on Black Holes and reported on everything from simulation universes to dancing cockatoos. He looks after the magazine’s and website’s news sections and makes regular appearances on the Instant Genius Podcast.