Lyme disease can spread to people via ticks
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An antibiotic that is commonly used to treat pneumonia rid mice of Lyme disease at a dose 100 times lower than the standard antibiotic therapy. This smaller dose, combined with the drug’s targeted action against the infection, meant the animals’ gut microbiomes were largely unaffected.
Lyme disease is caused by bacteria in the genus Borrelia that mainly spread among birds and small rodents, but people can get infected via the bites of ticks that have fed on the blood of such animals. Infections commonly lead to flu-like symptoms and a “bull’s-eye” rash. If untreated, they can cause serious long-term complications, such as fatigue and aches.
Standard treatment involves taking a high dose of the antibiotic doxycycline twice daily for up to three weeks. This stops bacteria from making the proteins they need to survive, but it doesn’t selectively target Borrelia species. “It wreaks havoc on the normal [gut] microbiome,” says Brandon Jutras at Northwestern University in Illinois.
Looking for a more selective alternative, Jutras and his colleagues first tested how effectively more than 450 antibiotics, all approved by the US Food and Drug Administration, could kill Borrelia burgdorferi – the most common type of Lyme disease-causing bacteria – in a lab dish.
They then assessed how the top-performing drugs affected the growth of harmless or beneficial bacteria that are commonly found in the guts of people and mice, such as certain strains of Escherichia coli. This revealed that piperacillin, an antibiotic that is related to penicillin and is commonly used to treat pneumonia, most selectively targeted B. burgdorferi.
Next, the researchers injected 46 mice with B. burgdorferi. Three weeks later, they treated the animals with varying doses of either doxycycline or piperacillin twice a day for one week. The researchers found no signs of infection in the mice that received either a high dose of doxycycline or as little as a 100-fold lower dose of piperacillin.
They also analysed stools from the mice before and after the antibiotic treatment and found that low-dose piperacillin had almost no effect on the levels of bacteria other than B. burgdorferi in the gut, whereas high-dose doxycycline heavily altered the gut microbiome.
This is probably because a lower dose of antibiotic has less of an effect on gut microbial diversity, and because of piperacillin’s targeted action. “With piperacillin, we found it’s targeting a particular protein that’s essential for B. burgdorferi, but not other bacteria, to survive, so it’s remarkably efficient at killing this Lyme disease agent at low concentrations,” says Jutras. This may help to preserve a healthy gut microbiome, which has been linked to a long, disease-free life.
But mice can respond differently to antibiotics than people do, says John Aucott at Johns Hopkins University in Maryland. For instance, they often break down the drugs faster, which can alter their effectiveness. Jutras’s team hopes to test piperacillin in human Lyme disease trials within the next few years.
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