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New superbug-fighting antibiotic discovered up humans' noses

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The nose knows

MRSA
NIAID/NIH

Believe it or not, some of us are carrying drug-resistant bacteria around in our noses; these colonies make infection more likely. But scientists have discovered a new weapon to use against these bugs — and it also lives in your nose.

It may be years before the new compound comes to market, but its discovery, published in the journal Nature, points to the value of an untapped resource for antibiotics. That resource, of course, is the human body. And new antibiotics are crucial for fighting drug-resistant bugs like MRSA, a variant of the Staphylococcus aureus, or staph, that doesn’t respond to a major class of antibiotics. The drug detailed in Nature not only fights MRSA, it can knock out a wide range of other bacteria.

We carry colonies of bacteria in our noses

Most antibiotics have been isolated from bacteria that live in soil, but finding new antibiotics from this source has proven difficult. Since the 1980s, no new classes of antibiotics have been discovered. The bacteria that live on and inside our body, however, haven’t been explored as much as soil has. Previous studies showed that certain bacteria that live in or on the human body had the genes needed to potentially make antibiotics. But today’s study is the first one to zero in on a particular bacterium that lives inside people’s nostrils, called Staphylococcus lugdunensis. The study demonstrates that this bacterium produces a new peptide antibiotic, named lugdunin, that’s part of an entirely new class of antibiotics.

"Lugdunin is just the first example," says study co-author Andreas Peschel, a microbiologist at University of Tübingen in Germany. "Maybe it’s just the tip of the iceberg."

Thousands of bacteria can be found everywhere on our bodies, from our skin to our guts. The nose is a breeding ground for many of them, including S. aureus, which is found in about 30 percent of the human population. From the nose, however, S. aureus can spread through the blood to the rest of the body, causing life-threatening infections. That’s particularly dangerous for hospital patients, who are recovering from surgeries or already have a weak immune system.

S. aureus can cause life-threatening infections

So what happens in the noses of the remaining 70 percent of the human population, who don’t carry S. aureus? To figure that out, the researchers swabbed the nostrils of 90 study participants and analyzed their microbiome. What they found surprised the researchers themselves: a particular type of bacterium, S. lugdunensis, created a compound that prevented the growth of S. aureus. "We did not start with the intention to identify a new antibiotic," says Peschel. "That was completely unexpected."

The scientists then silenced certain genes in S. lugdunesis until it no longer had any effect on S. aureus; that showed the researchers which genes were necessary to produce the lugdunin antibiotic. After synthesizing it, researchers tested how lugdunin works by infecting the skin of several mice with S. aureus. Next, they applied lugdunin on the mice — and those S. aureus colonies were either reduced in number or killed off entirely in all the mice except for two. (Those two, apparently, licked the antibiotic off their skin.) The researchers noted that lugdunin is also effective against drug-resistant Enterococcus bacteria, as well as MRSA, which kills about 20,000 Americans each year. Most importantly, lugdunin is not prone to causing resistance in S. aureus — which bodes well for the new class of antibiotics. With 10 million people predicted to die each year because of antibiotic-resistant infections by 2050, strong antibiotics is what we need.

The next step was checking out humans’ noses. Scientists swabbed the nostrils of 187 hospitalized patients to look for both S. aureus — the human-threatening bug — and S. lugdunensis, the antibiotic-generating one. Patients who didn’t have S. lugdunensis making a home in their noses carried S. aureus almost 35 percent of the time; patients with S. lugdunensis, though, had S. aureus just 6 percent of the time. That suggests that the new antibiotic could be used to "decolonize" the noses of at-risk hospital patients to decrease the risk of infections. Patients’ noses have already undergone S. aureus cleanups, but the practice has been controversial because it increases drug resistance. "These people are not sick, so it’s controversial to treat them with antibiotics," says Kim Lewis, the director of the Antimicrobial Discovery Center at Northeastern University, who didn’t work on the study.

"Resistance will develop, it’s inevitable."

The same problem might arise with lugdunin, however, warns Brad Spellberg, a professor of clinical medicine at the University of Southern California, who did not take part in the study. Even though no resistance was shown in the study, bacteria will learn to fight lugdunin in the future. "That is a naturally produced substance by an organism that’s been competing in its niche for millions, if not billions, of years," Spellberg says. "Resistance will develop, it’s inevitable."

The new compound also isn’t effective against certain bacteria like E. coli and pseudomonas, which are very dangerous and claim thousands of lives worldwide every year, says Melinda Pettigrew, a professor of epidemiology at the Yale School of Public Health. Humans are running out of drugs for those infections, too. Limited as its uses might be, lugdunin looks very promising and might eventually be developed into an antibiotic that will work in humans, Pettigrew says. The study is also a "proof of principle paper" that shows that looking at the human microbiome can successfully lead to finding new antibiotics — and will hopefully inspire other researchers to look a little closer to home in the future.