Hide from the immune system
When Egon Bech Hansen sees enzymes, he sees beauty. Having researched enzymes for 40 years, he finds that they are beautiful in themselves, but he also sees correlations which have pulled his normal expertise in foods such as camel milk and yogurt in a new direction that incorporates clinical treatment.
A protease (enzymes that break down protein) grows on the outside of the streptococcal bacterium. In yoghurt, the protease cleaves some of the milk’s proteins, allowing the bacterium to grow and convert milk sugar into lactic acid. Group A streptococcus exploit a similar enzyme to cleave signalling molecules from the body’s immune system, thereby avoiding that the infection-fighting immune cells are alerted.
“The bacteria become invisible to the body, so they can necrotize the tissue as they please,” explains Egon Bech Hansen.Handful of promising candidates
His experiments revealed that a handful of the 3,000 pharmaceuticals inhibit the protease that enables lactic acid bacteria to acidify milk. And as the enzymes in benign and malignant streptococci are so similar, he convinced researchers at the University of Limerick in Ireland who specialize in analysing bacterial protease to test whether these substances could inhibit the enzyme from Streptococcus pyogenes.
Six of the substances could, and hopefully some of them can be used to deactivate the enzyme and make the streptococcal bacteria visible to the immune system, so that the body itself will be able to fight the flesh-eating bacteria.
“There is no guarantee that it will work, but we’ve found some good candidates,” says Egon Bech Hansen and continues:
“What’s so exciting is that it’s a whole new way of treating infections. If we do a test on an agar plate to determine whether these pharmaceuticals inhibit the bacterium, nothing happens, because there is no immune system on an agar plate. So they aren’t antibiotic in the classical sense. But we make sure that the immune system detects the bacteria and hopefully fights the infection itself.”
The preliminary results are so promising that DTU has applied for a patent for Egon Bech Hansen’s screening method. In order to extend the list of candidates, Egon Bech Hasen is screening an additional 10,000 pharmaceuticals, including medicines that have not yet been launched on the market. The candidates will then be analysed further at the University of Limerick, where the researchers will study whether the pharmaceuticals have also inhibited the so-called virulence factor of streptococcal bacteria, which makes the bacterium pathogenic.
Although invasive group A streptococcus is a relatively rare infection, it is estimated that it kills 150,000 people worldwide every year. In Denmark, there are about 150 cases a year on average, but this year has seen a streptococcal epidemic where the number of cases has been 3-4 times higher than normal. From November to July, as many as 76 people died from invasive group A streptococcus, according to Statens Serum Institut (SSI), whereas the number is normally 20-25 annually. SSI concludes that the drastic increase is due to a new variant of group A streptococcus and reduced immunity following the coronavirus lockdown.
Other countries such as France, Ireland, the Netherlands, Sweden, and the UK have also seen a sharp increase in the number of cases of invasive group A streptococcus during the winter.
Egon Bech Hansen hopes that his discovery can help save human lives. He envisages that it will be possible to give the drug preventively to vulnerable groups such as children and the elderly, when, for example, they have a dirty wound and risk developing a streptococcal infection.Faster market launch
If it turns out that an existing pharmaceutical can knock out the enzyme in the streptococcal bacterium, Egon Bech Hansen estimates that a treatment could be developed within just a few years.
"If we find that an approved pharmaceutical, such as a headache tablet, can prevent streptococci from becoming necrotizing, it should be faster to get it onto the market,” says Egon Bech Hansen.
However, the challenge is that the development of pharmaceuticals for treatment of rare infections is not necessarily a lucrative business for pharmaceutical companies, and they will therefore be reluctant to conduct further research into this. But this does not discourage Egon Bech Hansen.
"I’m pretty confident that if we obtain funding to continue the research, we will be able to find a treatment,” he says.