The discovery suggests that the human microbiome may be a rich source for future drugs
Humans, and the microbes that live inside us, could be the source of the next generation of antibiotics.
German researchers just discovered an antibiotic produced by bacteria that inhabit our noses. This new antibiotic can kill MRSA, the poster child for drug resistance and the culprit behind the most pernicious hospital acquired staph infections.
“Our study can help to understand what we can do to eradicate these pathogens from the microbiota of healthy people,” said Andreas Peschel, lead author of the study.
Here’s how it works: Think of our bodies as garden beds, with bacteria as the plants. We used to think that all bacteria were weeds, invading and making us sick. To get rid of bacteria, we just hacked everything down.
“We’ve taken basically a ‘clear cutting’ approach to treating disease just whack ‘em all and hope that something good happens,” said Michael Gilmore, a professor of microbiology at Harvard Medical School who reviewed the study and is an expert in antibiotic resistance and drug discovery.
Instead, something bad happened: overuse and poor compliance led to antibiotic resistance. MRSA infection caused by staph that don’t respond to methicillin kills around 20,000 people each year. Around 30 percent of people have the bacteria species that includes MRSA, S. aureus, in their noses right now. The authors point out that the nose is a common entryway for MRSA to get into the human body.
“Some people are prone to staph infections and other people are relatively resistant,” Gilmore said. Part of that is our immune system, and part of it is the other microbes that we carry around with us.
And it’s those other microbes, the German team found, that strike MRSA dead.
A Native Species:
Scientists at the University of Tübingen sucked the bacteria-laden snot from 37 healthy people and cultured the different bacteria species they found in their samples. To figure out if any of the bacteria they’d found would help keep MRSA away, they planted S. aureus alongside the other snot species, and watched them grow.
The winner, another staph species called S. lugdunensis, was killing S. aureus. A small compound dubbed lugdunin.
When the researchers tested the new compound in mice, they could treat staph infections. Study author Bernhard Krismer pointed out that “the compound penetrated the tissue and also acted in the deeper layers of the skin,” a useful trick for treating deep-rooted staph infections that are the hallmark of MRSA.
And when they left S. aureus and lugdunin together for a month, S. aureus still hadn’t developed resistance to it, suggesting that lugdunin is really tough to beat, Krismer said.
The researchers then checked snot from hospitalized patients. Of 187 samples, all but one were colonized by either S. aureus or S. lugdunensis, but not both. The researchers think where one species grows, the other can’t.
And it’s all about the lugdunin. When the researchers messed up the lugdunin gene in S. lugdunensis, S. aureus had no trouble growing.
In other words, human gardens have a native plant that kills a potentially deadly weed.
The German researchers who performed the study have filed a patent for lugdunin and are hoping to work with pharmaceutical companies to develop it.
Super Bugs and Super Heroes:
In the clinic right now, “we’re using broad spectrum oral bioavailable drugs that are decimating our own microbiome in order to treat a tooth infection or an ear infection,” Gilmore said.
Gilmore thinks the time is right to rethink our antimicrobial strategy. This Nature study is a promising direction, he said.
“What I think the next era is, and I think we’re turning the corner on this, is effectively managing the association between microbes and humans in both health and disease,” he said.
For instance, doctors could focus more on applying antibiotics locally to just the infected area, especially in the case of infections that are easy to reach, like periodontal disease and ear infections. By selectively treating only serious infections, we might be able to stave off the next round of resistance.
The German researchers think there are tons of bacteria with secret powers waiting to be discovered super heroes to fight off super bugs. One comes from bacteria that naturally inhabit vaginal mucus.
But the newest work takes a step further by showing that S. lugdunensis can block MRSA from taking root in the body at all. “That’s a big deal,” said Michael Fischbach, the UCSF researcher who led the vaginal mucus findings, since preventing S. aureus from growing in the nostril is an important challenge in preventing staph infections (Fischbach works with several biopharma companies and sits on the board of directors of Achaogen, a company that’s developing antibiotics).
In addition to trying to develop lugdunin as an antibiotic drug, the new findings suggest that we might be able to seed specific parts of our bodies with commensal bacteria in the form of probiotics.
Currently, over the counter probiotics are made from bacteria that don’t normally inhabit humans, so they get digested. On the other hand, a probiotic made from commensal bacteria could stick around for a long time and alter the flora of whatever part of the body is out of whack. This is the idea behind fecal transplants.
However, Peschel said, “S. lugdunensis itself is maybe not the perfect probiotic bacteria that you would like to propagate in the nose of the risk patient who is immune-compromised” because this species occasionally makes people sick.”
Getting around that will take some tricks. For instance, the German researchers plan to make a GMO combining genes from S. lugdunensis and another, more benign bacterium.
While we’re still years away from seeing any of these natural killers or probiotics come to fruition in the clinic, the future is much less grim than previously thought.
On the other hand, it could be another quick respite in the ongoing arms race between bacteria and antibiotics.
While researchers are excited at the thought of site-specific probiotics, others worry that, once such treatments are used, pathogenic bacteria will figure out how to beat these antibiotics too.
“I wouldn’t bet against a wily bacterium like S. aureus,” Fischbach, the UCSF researcher, said.
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