Tag Archives: penicillin

Scientists sequence genome of Fleming’s original penicillin-producing fungus

A group of researchers successfully sequenced the genome of the mold that produced penicillin, the world’s first true antibiotic, using samples frozen alive more than fifty years ago. The team compared Alexander Fleming’s original sample of penicillium mold to two strains of mold now used to produce the substance today.

The freeze-dried Fleming strain from which the Penicillium fungus was grown and genome sequenced. Credit CABI.

Back in 1928, biologist Alexander Fleming noticed Penicillium mold growing in a culture of Staphylococcus aureus he was studying. It appeared the experiment was wrecked but Fleming noticed that where the mold grew, the bacteria didn’t. He later identified the chemical compound that was fatal to the bacteria and called it penicillin in honor of the humble mold.

Fleming froze samples of the mold that produced his first isolated samples of pure penicillin. More than 50 years later, a group of researchers at Imperial College London and the University of Oxford decided to look them up. They compared the samples with the genomes of two modern strains of Penicillium mold, now used in the United States.

“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 Penicillium, despite its historical significance to the field,” said Timothy Barraclaugh, co-author, in a statement.

The researchers found a subtle difference between the two genomes, which might help us better combat antibacterial resistance. Most antibiotics are based on chemicals that fungi or bacteria produce to defend themselves. If you get a dose of penicillin, it was likely produced by mold cultures, which are descendants of samples taken from moldy cantaloupes.

Over the years, antibiotics manufacturers bred their cantaloupe mold cultures to produce more penicillin. This means the genomes of modern industrial Penicillum mold are probably very different from their cantaloupe-eating ancestors.

The team looked at two sets of genes in particular. The ones that coded for chemicals called enzymes and the ones that control how much of an enzyme to make and when. They found that modern strains had more copies of the genetic instructions for making those enzymes, which meant those cells would make more enzymes and thus more penicillin.

While nature favors the traits that make mold more likely to survive and pass on its genes, artificial selection by humans cares about penicillin production over everything else. But Fleming’s mold and the modern strains used different versions of the enzymes that make penicillin. This could be due to evolution in the lab or because the strains are from different continents and evolved different enzymes.

If that’s the case, those different enzymes might produce different versions of penicillin. Still, there’s not enough data now to say exactly how the different enzymes impact the final product. The difference could lead to more efficient penicillin production, more effective penicillin, or a way to work around at least some of the resistance certain bacteria strains have evolved to the drug, the researchers believe.

“Industrial production of penicillin concentrated on the amount produced, and the steps used to artificially improve production led to changes in numbers of genes,” Ayush Pathak, lead author, said in a statement. “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.”

The study was published in the journal Scientific Reports.

Most people who think they have a penicillin allergy don’t — and it can be a problem

A new study has found that a surprisingly high number of people wrongly believe they are allergic to penicillin, and that might end up costing them somewhere down the line.

Within the US, some 10% of all patients believe they are allergic to penicillin — but in reality, 90% of these people aren’t. This means that every year, millions of people can end up taking alternative antibiotics, which are more expensive and can destroy the body’s healthy bacterial flora. Furthermore, according to a study, which was carried out in the UK and published in the British Medical Journal, people with a penicillin allergy are 70% more likely to acquire a methicillin-resistant Staphylococcus aureus (MRSA) infection and have a 26% increased risk of Clostridium difficile-related colitis (C. diff.). This means that people who wrongly believe they are allergic to penicillin are needlessly subjecting themselves to additional infection risks.

The good news, researchers say, is that there’s a simple allergy test which can be carried out, but it needs to be more widely implemented.

People with an alleged penicillin allergy are typically given a prescription of broad-spectrum antibiotics which, as the name implies, cover a broad number of microorganisms, and can end up killing more things than they should — particularly, the body’s useful bacteria. Any imbalance in the body’s bacterial fauna can weaken the immune system and make it easier for other infections to take over — especially drug-resistant bacteria like MRSA.

Meanwhile, penicillin is a very targeted and potent drug, ideal for treating a particular set of infections.

“Penicillin-related drugs, that whole class … they’re very effective at killing, and they’re very targeted. So for some bacteria they’re still the best. Oldie but goody,” Kim Blumenthal, lead author of the new study and assistant professor of medicine at Harvard Medical School, told the Washington Post. “I have seen so many terrible, terrible outcomes” from C. diff. infections, Blumenthal said, including serious diarrhea, sepsis and death.

[panel style=”panel-default” title=”Penicillin” footer=””]Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming, and started being used to treat infections in 1942.

While the number of penicillin-resistant bacteria is increasing, penicillin can still be used to treat a wide range of infections caused by certain susceptible bacteria, including Streptococci, Staphylococci, and Clostridium.

An estimated 0.03% of the population have serious allergies to penicillin.[/panel]

Things can get even worse when targeted penicillin isn’t used. Using non-targeted, broad-spectrum antibiotics can breed the next generation of drug-resistant bacteria. According to the CDC, some 2 million people get infected with these pathogens every year. Among these, over 23,000 will go on to lose their lives as a result of the bacterial infection, which often leads to other complications. The World Health Organization has also identified drug-resistant pathogens as one of the main threats to human society, and already, some infections are becoming nigh impossible to treat — including gonorrhea.

Well, it sure used to at least.

It’s still not clear exactly why so many people wrongly believe they are allergic to penicillin but doctors have a few good ideas. For starters, many are diagnosed with the allergy as a child, and they grow out of the allergy — something which can happen but isn’t a guarantee by any means. Then, allergy means different things to different people. Essentially, an allergy is simply an exaggerated response of the immune system, but that can range from a minor rash to life-threatening issues. If a patient comes into the hospital suffering from a serious, potentially life-threatening condition, and his file says “allergic to penicillin,” doctors simply won’t give him the drug. But quite often, it could ultimately end up saving his life, with only a minor side effect. In most cases, researchers say, penicillin should only be avoided if the side effect is serious.

If you’ve been previously diagnosed with such a penicillin allergy, but more than 10 years have passed, doctors suggest to get re-tested.

Journal Reference: Blumenthal et al. “Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study.” doi: https://doi.org/10.1136/bmj.k2400