Drug treatment for Lyme disease could lead to its eradication

By Michael Le Page

Microscopic image of Borrelia burgdorferi bacteria

Cultura Creative RF/Alamy

The discovery that a chemical is deadly to the bacterium that causes Lyme disease but harmless to animals might allow the disease to be eradicated in the wild.

“Lyme disease is well-positioned to be eradicated,” says Kim Lewis at Northeastern University in Boston. “We are gearing up, the first field trial will be next summer.”

Lyme disease is caused by a bacterium called Borrelia burgdorferi that lurks in wild mice. Ticks that feed on the mice become infected and can infect other animals, including people.

The disease is a growing problem in North America, Europe and Asia. It initially causes a characteristic “bullseye” rash and a flu-like illness. If untreated, it can lead to serious long-term problems, such as Lyme arthritis.

At present, it is treated with antibiotics such as doxycycline that kill a wide range of bacteria. However, this disrupts the gut microbiome, causing symptoms such as diarrhoea, and can also lead to more antibiotic resistance.

Now, Lewis’s team has found that a compound called hygromycin A is completely harmless to animals and has little effect on most bacteria, but is extremely deadly to spirochaete bacteria such as B. burgdorferi.

Spirochaete bacteria have a corkscrew shape that enables them to burrow into tissues. They also cause diseases such as syphilis, says Lewis. “They are pretty nasty pathogens.”

In animal tests, the team didn’t observe any harmful effects of hygromycin no matter how high the dose. “It is unusually safe,” says Lewis.

A company called FlightPath is now filing in the US for the initial go-ahead required before the chemical can be tested in people.

Hygromycin could also potentially be used as a treatment for syphilis, particularly because this bacterial infection is evolving resistance to standard treatments.

What’s more, Lewis’s team has shown that feeding baits laced with hygromycin to mice can clear B. burgdorferi infections. In theory, dropping such baits could eradicate Lyme disease from whole areas or even entire countries.

A field trial done a decade ago with doxycycline baits was successful, says Lewis. But the widespread use of the chemical for this purpose is undesirable because it could lead to many microbes evolving antibiotic resistance.

By contrast, Lewis’s studies suggest it is extremely difficult for B. burgdorferi to evolve resistance to hygromycin. The chemical resembles essential nutrients that spirochaetes cannot make themselves and take up using a specific transporter, so mutations that block the take-up of hygromycin would also deprive spirochaetes of these nutrients.

Lewis says his team isn’t the first to discover the value of hygromycin. It was studied as a potential treatment for a pig disease in the 1980s but abandoned.

Vaccines against Lyme disease are also being developed, but eradicating the disease would be an even better option.

Journal reference: Cell, DOI: 10.1016/j.cell.2021.09.011

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