Researchers have discovered a new antibiotic — and it belongs to a brand new class.The compound, named teixobactin, treated a wide variety of infections in mice, including staph and blood infections, reports a study published in Nature today. And because of teixobactin's molecular structure, researchers believe that developing resistance to the compound will be difficult — an important characteristic in the face of increasingly resistant bacterial infections worldwide.
Teixobactin probably couldn't have been discovered until now
Teixobactin probably couldn't have been discovered until now. Normally, the bacteria used to produce antibiotics are grown in sterilized laboratory settings. But only 1 percent of environmental microorganisms can be grown successfully in petri dishes, says Kim Lewis, a microbiologist at Northeastern University and a co-author of the study, in a press call. So researchers were limited to a tiny portion of the available bacteria.That's why researchers at Northeastern came up with a way to grow "uncultured bacteria" in soil, their natural environment — something scientists previously thought would be too difficult to achieve. Then, the researchers screened 10,000 soil bacterial strains and identified 25 that might be capable of producing new antibiotics. And of that set, Lewis said, teixobactin was the most promising.
"Early on we saw that there was no resistance development to teixobactin," Lewis said. "We also find that teixobactin had good efficacy in several animal models of infection," without causing any visible side-effects to the doses tested — a characteristic that makes it "a promising drug candidate."
"there was no resistance development to teixobactin."
The antibiotic discovery comes at a time when many bacterial infections have become difficult to treat. Approximately 23,000 people die in the US each year because of resistant strains. In response, health officials have asked that antibiotics only be used when absolutely necessary — a move that has contributed to a decline in antibiotic research, and growing disinterest from the pharmacological industry. "Pathogens are acquiring resistance faster than we can introduce new antibiotics," Lewis said. And "we now have pathogens, such as strains of Mycobacterium tuberculosis, that are resistant to all available antibiotics." The researchers therefore hope that the announcement of a new antibiotic candidate be the kick in the pants that the pharmaceutical world needs to start searching for new compounds again.
Teixobactin works by breaking down bacteria's cell wall, triggering the cell's death — which is "a particular Achilles heel for antibiotic attack," said Tanya Schneider, a biochemist at Connecticut College and a co-author of the study. Because bacteria can't easily modify their cell walls to resist antibiotics, the drug won't spur resistance as readily, Schneider says.
Teixobactin works by breaking down bacteria's cell wall
The researchers were able to use teixobactin to successfully treat mice with blood infection, lung infections, and staph infections. Unfortunately, the compound wasn’t able to treat infections caused by E. coli because this type of bacteria — commonly referred to as "Gram-negative bacteria" — is surrounded by an outer membrane that prevents access to the drug's target.
Henry Chambers, an infectious disease researcher at the University of California, San Francisco, who didn’t participate in the study, thinks the researchers’ new approach is interesting. But the fact that the antibiotic isn’t effective against most Gram-negative bacteria is slightly disappointing. "There are now plenty of drugs for infections caused by Gram-positive," he said, "and the more pressing need is for resistant Gram-negatives."
Chambers also cautions against getting too excited about the idea of a new antibiotic. It’s "too early to get excited for yet to be proven clinical utility," Chambers says. And even if the drug is approved for human use, it won’t solve the current problem of widespread antibiotic resistance — a problem that stems from overuse in both medicine and food production. "If an antibiotic is used enough, resistance ultimately will emerge." For example, although it took 40 years for resistance to develop against vancomycin — another antibiotic that works in a similar way — resistance did eventually occur. Still, if teixobactin is approved for human use in a few years, that will be good news, Chambers says. "New potent and effective antibiotics belonging to a novel class are welcome, even for Gram-positives."
Getting the antibiotic to market will take at least five years
A lot can go wrong during drug development, though. So far, producing large quantities of the bacteria that produces teixobactin hasn’t been too difficult —but because the drug has yet to be tested on humans, it’s difficult to predict how well it will do in the long run. Before human trials can take place, the researchers would like to find out if they can produce the drug synthetically, rather than from bacteria — a process that might be more efficient. They also want to improve the drug’s effectiveness. That, Lewis said, will take about two years. And then they will need at least another three years to test teixobactin on humans. Still, the antibiotic discovery is encouraging, because the method used to discover it could lead to other new discoveries, too.
"The discovery of compounds like teixobactin that came from uncultured bacteria suggests that this is a promising source in general for antibiotics," Lewis says. "And that it has a good chance of helping revive the field of antibiotic discovery."