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This Is What We Can Learn From The Genome Of Alexander Fleming’s Original Penicillin Mold – Forbes

Researchers recently sequenced the genome of the mold that produced the world’s first true antibiotic, penicillin. When biologists Ayush Pathak and Timothy Barraclough (both of Imperial College London) and their colleagues compared DNA from biologist Alexander Fleming’s original sample of Penicillum mold to the genomes of two strains of mold being used to produce modern penicillin in the US., they found that the strains produce the drug in slightly different ways. That could have some implications for making modern antibiotics.

No Lab Contamination, Just Happy Accidents

We owe the antibiotic age, in part, to a lab accident in 1928. When biologist Alexander Fleming noticed Penicillum mold growing in a culture of Staphylococcus aureus he was studying, it looked like his experiment was wrecked. However, Fleming noticed something interesting; where the mold grew, the bacteria didn’t.

People had known for millennia that some types of mold, including Penicillum, could be used to treat infections. But Fleming took things a step further and figured out exactly which chemical compound the mold produced that was fatal to the bacteria. He called it penicillin, and the world was never the same again.

Fleming froze samples of the mold that produced his first isolated samples of pure penicillin. More than 50 years later, Pathak, Barraclough, and their colleagues decided to look them up. “We originally set out to use Alexander Fleming’s fungus for some different experiments, but we realized, to our surprise, that no one had sequenced the genome of the original Penicillum, despite its historical significance to the field,” said Barraclaugh in a statement to the press. They published their results in the journal Scientific Reports.

When Pathak, Barraclough, and their colleagues compared the genome of Fleming’s Penicillum mold with the genomes of two modern strains of Penicillum mold, now used in the U.S., to produce penicillin for pharmaceutical companies, they found a subtle difference. And that difference, according to Pathak, Barraclough, and their colleagues, might offer some hints about combatting antibacterial resistance.

Growing Mold For Fun And Profit

Most antibiotics are based on chemicals that fungi or bacteria produce to defend themselves against other microbes. If you receive a dose of penicillin today in the US, it was probably produced by Penicillum mold cultures in a commercial lab – and those cultures are the descendants of samples originally taken from moldy cantaloupes. Please don’t try that at home (or at least take good notes).

Over the years, antibiotics manufacturers bred their cantaloupe mold cultures to produce more penicillin, in pretty much the same way farmers might breed higher-yield corn, wheat, or apple trees. That means the genomes of modern industrial Penicillum mold are probably very different from their cantaloupe-eating ancestors. And comparing those modern genomes to the genome from Fleming’s original sample sheds some light on exactly how they’re different.

Pathak, Barraclough, and their colleagues focused on two sets of genes in particular: the ones that coded for chemicals called enzymes, which cause the chemical reactions that actually make penicillin, and the ones that control how much of an enzyme to make and when to do it. They found that modern Penicillum strains had more copies of the genetic instructions for making those enzymes, which meant those cells would make more enzymes and thus more penicillin.

That’s not too surprising. Nature would have favored whatever set of traits made a bit of mold more likely to survive and pass on its genes. Artificial selection by humans, however, cared about penicillin production at the expense of pretty much everything else about the mold as an organism.  

Another Moldy Mystery To Solve

But Fleming’s mold and the modern strains also used slightly different versions of the enzymes that actually make penicillin. That could be the product of evolution in the lab, or it could be because the strains came from different continents – Fleming’s lab in the UK, and cantaloupes in the US – and had each evolved different enzymes to deal with their own local microbes.

If that’s the case, then those different enzymes might produce slightly different versions of penicillin. There’s not enough data at this point to say exactly what the different enzymes mean for the final product. It’s possible that the difference could lead to more efficient penicillin production, more effective penicillin, or a way to work around at least some of the resistance some bacteria have evolved to the drug.

It’s important to note that this is still just speculation, so don’t get too excited – but Pathak pointed out in a statement to the press that in the rush to produce more penicillin faster, we may have overlooked useful ways of making it better, or at least different.

“Industrial production of penicillin concentrated on the amount produced, and the steps used to artificially improve production led to changes in numbers of genes,” he said. “But it is possible that industrial methods might have missed some changes for optimizing penicillin design, and we can learn from natural responses to the evolution of antibiotic resistance.”

To know whether that’s the case, biologists will first need to understand whether the different enzymes produce the same chemical in different ways, or if there’s some sort of difference in the final product. If there is a difference, the different versions will need to be tested against bacteria to see what happens. In the meantime, the important lesson is: wash your cantaloupe really well before you eat it.

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