From a soil sample harvested in a grassy meadow in Maine, a team led by a Northeastern University researcher has discovered a completely novel antibiotic.
The new antibiotic, teixobactin, kills an array of pathogens, and in early laboratory tests bacteria did not develop resistance to the drug.
Outside researchers said that the most exciting thing about the new finding, published Wednesday in the journal Nature, was the possibility that researchers might now efficiently scour ordinary soil samples and other sources of bacteria in the search for leads in developing new antibiotics. This will be a powerful tool for scientists and doctors who are running out of options in an ever-escalating arms race against “superbugs” that rapidly develop resistance to existing therapies.
“There’s maybe, potentially, two orders of magnitude or 100 times as many classes of antibiotics that we haven’t discovered yet,” said Dr. Michael Kurilla, director of the office of biodefense, research resources, and translational research at the National Institute of Allergy and Infectious Diseases, who was not involved in the study. “This is where everything has to start, and this is as promising and exciting as we’ve seen in awhile.”
To understand why the technique is so powerful, it’s important to understand where antibiotics come from. The lifesaving drugs that created a public health revolution beginning in the 1940s have their roots in the warfare that occurs between bacteria competing against one another in the environment. Antibiotics happen to kill the pathogens that infect people so effectively because they are the weapons that bacteria have evolved to gain an advantage against other bacteria.
For years, soil bacteria were an important source of new antibiotics, but by the 1960s that resource had been largely tapped out. But the vast majority of bacteria -- about 99 percent -- do not grow in a laboratory dish. That means that scientists had studied only a tiny fraction of the natural diversity of methods that bacteria have evolved to kill one another when they were trying to identify new possible drugs.
In the study published Wednesday, researchers from Northeastern, a Cambridge startup company called NovoBiotic Pharmaceuticals, and Germany described using a technique that allows them to grow those bacteria. Using the device, called the iChip, they separated individual bacteria cells into wells. Then they covered the chip with a membrane that kept the bacteria inside -- and stuck the whole assemblage back in the soil. That allowed the previously uncultivatable bacteria to grow.
They screened 10,000 of those bacteria against the pathogen that causes staph infections and found their most promising candidate was a very large molecule.
“I must tell you, my first impression about this compound was that it is boring,” said Kim Lewis, director of the Antimicrobial Discovery Center at Northeastern. That’s because the bacteria that cause tuberculosis and staph infections did not develop resistance to the molecule, which is often a sign that the possible drug is simply toxic to all cells.
Then Lewis and his colleagues tested its toxicity against mammalian cells and found that it didn’t kill them. They also discovered that teixobactin had a new way of killing bacteria, by inhibiting the building of the cell wall.
The name of the drug plays off the Greek word teixos, for wall, since it inhibited the building of the cell wall.
The search for new antibiotics has led scientists to think about finding bacteria that live in exotic places, such as the sea floor, but the new technique could enable them to reexamine more ordinary sources.
“Here it is, something as simple as bacteria that are circulating that we haven’t been able to grow them -- and now we can,” said Dr. Stuart Levy, director of the Center on Adaptation Genetics and Drug Resistance at Tufts University School of Medicine. “I think it’s fascinating what they’ve accomplished.”
He and others said that it was premature to declare that bacteria would absolutely not develop resistance to teixobactin, but that it was a promising candidate nonetheless.
But it is just one in an array of efforts to develop new ways to halt infections. Other approaches span the gamut, from trying to chemically modify existing antibiotics to creating bacteria-attacking viruses that will preferentially kill the pathogens that carry antibiotic resistance genes.
Timothy Lu, an associate professor of biological and electrical engineering at the Massachusetts Institute of Technology has been working on creating those smart viruses and said that he thinks the future will depend on multiple approaches.
“Regardless of how many new compounds we can find, if we are dosing people with broad spectrum agents that’s inevitably going to lead to resistance cropping up in the long run,” Lu said.
Dr. Henry Chambers, a professor of medicine at the University of California, San Francisco, said that the trend has been for small biotechnology companies to develop new antibiotics, but there has been growing interest in the area as the need for new drugs has grown and as legislative efforts have attempted to create incentives for companies developing antibiotics.
Merck announced it would buy Lexington-based Cubist Pharmaceuticals for $9.5 billion last year.
Lewis, who is a founder of NovoBiotic Pharmaceuticals, said that there is still work to be done to make teixobactin more soluble and test its safety, so clinical tests are several years away.