New antibiotic silences genes to single out bad bacteria
Antibiotics are effective at killing bacteria (for now, at least), but they aren't very picky, indiscriminately wiping out both good and bad bacteria. This can upset the fragile balance of your microbiome, which is increasingly being linked to general health and wellbeing. Now, researchers at Penn State have developed a new approach to make a drug that can single out a specific, opportunistic bacteria known as C. difficile.
Strange as it sounds, in some cases taking antibiotics can cause a bacterial infection. That's because they effectively carpet-bomb your insides, killing the good bacteria that are vital to your health alongside the bad bugs. C. difficile is one of the latter group, and although it's normally kept in check by good bacteria, once they're out of the picture it's adept at running amok and causing infection in the colon.
To prevent that, the Penn State team set out to develop new antibiotics that can single out C. difficile while leaving the good bugs alone.
"Ideally, a treatment for C. difficile would have no effect on other bacteria," says David Stewart, co-principal investigator on the study. "These drugs are organism specific, meaning that they target only one kind of bacteria, kind of like smart antibiotics. They're precise. And that's especially important with C. difficile infections because this bacteria is uniquely, selectively advantaged to exploit ecological disturbances in the human gut."
The new drugs are built around what's known as antisense therapy, meaning they prevent bacteria from expressing certain genes that are vital to their survival. That way, antibiotics can be precisely tuned to zero in on genes that are unique to the target species.
"Our antisense antibiotics contain genetic material which is complementary to bacterial genetic material, so we designed our genetic material to target specific genes in C. difficile," says Stewart. "And when our genetic material binds to the bacterial genetic material, it prevents the expression of bacterial genes. And that can cause C. difficile to die."
The researchers tested three different versions of the drug, which used different carrier compounds to transport the active ingredient to the bacteria. The tests helped the team determine how much of the drug was needed to kill the C. difficile, as well as make sure that it didn't affect good gut bacteria or harm human colon cells.
"We were able to show that these drugs can zero in on and kill C. difficile bacteria while leaving other bacteria alone," says Arun Sharma, co-principal investigator on the study. "We're still working to refine these drugs and make them even better, with the eventual goal of testing them clinically."
After testing the three different carriers, the researchers found that one in particular, named CYDE-21, was the most effective. It was found to carry the drug well, while minimizing its harm to other bacteria or human cells. The researchers say they're now working to refine these carriers to prepare for eventual animal studies.
The research was published in the Journal of Antibiotics.
Source: Penn State