You know that sinking feeling. Your bladder is feeling constantly full, announcing the return of your urinary tract infection. Or your baby is screaming again, just as he screamed the last time he had an ear infection. Or your teenager says, “My throat is hurting — feels like the strep is back.”
Certain bacterial infections have an infuriating tendency to recur even after they’re treated with antibiotics, and scientists have determined a key reason why: A few of the bugs go into a dormant state that protects them from antibiotics. Known as “persisters,” they are the bacterial villains behind those pesky infections that just keep coming back.
Today in the journal Nature, researchers report discovering a surprisingly sweet method to get rid of those nasty persisters. From the Boston University press release:
James Collins, a pioneering researcher in the new field of systems biology and a MacArthur Genius, says: “You know the old saying: ‘a spoonful of sugar makes the medicine go down?’ This is more like ‘a spoonful of sugar makes the medicine work.’
Dr. Collins, a professor of Biomedical Engineering at Boston University who is also a Howard Hughes Medical Institute investigator and a core faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, is talking about his recent development of an effective, low-cost – and surprising – way to treat chronic bacterial infections, such as staph, strep, tuberculosis, and infections of the urinary tract.
He and his team of scientists discovered that a simple compound – sugar – dramatically boosts the effectiveness of first-line antibiotics. Their findings appear in the May 12 issue of Nature (online May 11th).
Dr. Collins, 45, who is also a founder of the new field of synthetic biology, has a personal interest in this research. His 71 year old mother, Eileen Collins, was hospitalized several times in recent years with recurrent bouts of a serious staph infection. Doctors treated her with multiple intravenous antibiotics and still the infection could not be killed. It was his mother’s suffering that added urgency to Dr. Collins’ research.
You’ve probably heard about the looming problem of bacteria that have become resistant to antibiotics largely because the drugs are so heavily prescribed these days. Persisters are different, the release explains:
Unlike antibiotic-resistant bacteria, whose ability to withstand drug treatments is based on genetic mutations fostered by exposure to drug treatment, persisters are genetically identical to the other members of their bacterial community. What separates them from the pack is their ability to switch into power-save mode.
Dr. Collins’ research team has now discovered an inexpensive and effective way to rouse these bacterial sleepers, using a simple weapon – sugar – to stimulate them into an active state in which they are just as vulnerable to antibiotics as the others in their community.
Dr. Collins’ approach consists of adding sugar to the antibiotic. The sugar acts as a stimulant, essentially turning on normal bacterial responses, such as dying when confronted by a killer antibiotic.
Using this strategy on E. coli bacteria, a common cause of urinary tract infections, the team was able to eliminate 99.9 per cent of the persisters within just two hours – compared to no effect without sugar. The approach was similarly effective in killing Staphylococcus aureus bacteria, which cause sometimes deadly staph infections.
“Our goal was to improve the effectiveness of existing antibiotics, rather than invent new ones, which can be a long and costly process,” says Collins’ Boston University PhD student, Kyle Allison, who was the first author on the study.
The findings have the potential to improve the lives of untold numbers of people who struggle with nagging infections, while also reducing healthcare costs substantially.
So how would this work? I asked Jim Collins today — with hope in my voice — whether we will all soon get to wash our antibiotics down with sugary drinks and candy.
Jim emphasized that his team has not yet tried the sugar method in humans, but in mice receiving intravenous antibiotics, it worked to mix the sugar in with the antibiotics in a solution. “We’re also exploring whether a similar effect could work via ingestion,” he said.
“The notion of taking spoonfuls of sugar is really more to give the public an intuitive sense of what the discovery is,” he said. “And it is potentially the eventual therapeutic implication, but right now we don’t have data to support that.”
Jim Collins and his team are currently exploring how the sugar method might work on tuberculosis infections, and expect that it may work with other bacteria as well.
Sugar seems like such a simple intervention; why, then, had it not been discovered as an antibiotics booster before? Jim’s reply:
“It’s a really good question. I think we, as scientists, tend to narrowly focus, in many cases, on a range of questions that’s dictated by what we know and what we’re able to study. Persisters were discovered several decades ago, but it’s only over the last five or six years that scientists have begun to study them. And that’s because they generally exist in very small numbers — out of a bacterial culture only 1 in 1000 or 1 in 10,000 will be persisters — and the technology has only now come about that enables us to study them at some level.
Over the last five or six years, people have primarily focused on trying to understand: How are they formed? We, as bio-engineers, have also been exploring that same topic, but we flipped it on its head two years ago and said: ‘Okay, can we figure out a way to kill these guys off? Could we wake these guys up? ‘ We took a South Boston approach: Could we get these guys off the ground and then punch them and knock them back down?
The idea is that antibiotics primarily work on dividing cells, and the reason these dormant cells are resistant is that they’re not dividing. And the easiest way to wake cells up is give them sugars.”
The added sugars did not enhance the effects of most antibiotics, but they did work on one category. Jim and his team worked backward from that success, and figured out that the sugars were hitting specific aspects of the cell metabolism, triggering processes that allowed the cell to take up the antibiotics.
That understanding opens the way to exploring whether other chemicals might work to enhance the effects of other antibiotics, he said.
For more on Jim’s findings, check out the Globe’s Carolyn Johnson’s excellent report here.