‘Nose-y’ Bacteria Could Yield A New Antibiotic to Fight Drug-Resistant SuperBugs: lugdunin

Once scientists grew these Staphylococcus lugdunensis bacteria in a lab dish, they were able to isolate a compound that’s lethal to another strain commonly found in the nose that can make us sick — Staphylococcus aureus.

by Carolyn Beans

With antibiotic-resistant super bugs on the rise, researchers are on an urgent hunt for other bacteria that might yield chemicals we can harness as powerful drugs. Scientists once found most of these helpful bacteria in soil, but in recent decades this go-to search location hasn’t delivered.

Now, researchers at the University of Tübingen in Germany say that to find at least one promising candidate, we need look no further than our own noses.

The scientists report Wednesday in the journal Nature that a species of bacteria inside the human nose produces a substance capable of killing a range of bacteria, including the strain of drug-resistant Staphylococcus aureus known as MRSA.

The Tübingen team is delighted with their find. “It was totally unexpected,” says study author Andreas Peschel.

The scientists already knew that S. aureus lives in the noses of about 30 percent of humans, usually without causing harm — most people never know they are carriers of the bacterium. But if the body becomes compromised (whether by surgery, physical trauma, an underlying illness or suppressed immune system) the little cache of S. aureus in the nose can suddenly launch an attack against its human host. And if the strain of bacteria is MRSA, that infection can be lethal.

The scientists wondered how 70 percent of human noses are able to avoid harboring S. aureus. They guessed it might have something to do with neighboring bacteria.

So the researchers pitted 90 different human nasal bacteria in one-on-one battles with S. aureus in the lab. Indeed, one of these bacteria — Staphylococcus lugdunensis — prevented the dangerous pathogen from growing.

They then studied the arsenal of chemicals that S. lugdunensis produces until they found one that stops S. aureus in its tracks – a new antibiotic that they named lugdunin.

Follow-up work confirmed that lugdunin can treat S. aureus skin infections in mice, and limit the spread of S. aureus in a rat’s nose.

Lugdunin may already be keeping S. aureus out of our noses. In a group of 187 hospitalized people, the same scientists found S. aureus in the noses of just 5.9 percent of people who also harbored the lugdunin-producing bacteria, but 34.7 percent of those who didn’t.

Other recent studies have shown that bacteria living in humans carry genes that have the potential to make antibiotics. The Tübingen study takes those results a step further by showing that an antibiotic produced by a bacterium in the human nose can successfully treat an animal’s infection.

“This paper is a really nice follow-up,” says Dr. Nita Salzman, a pathologist at the Medical College of Wisconsin. “It’s a sort of proof of principle that the microbiome is a good source for novel antibiotics.”

The researchers have applied for a patent for lugdunin, but say that the prototype antibiotic is still many years away from being ready to treat humans.

The really important contribution of this study is not lugdunin itself, says microbiologist Kim Lewis of Northeastern University, but rather the new approach for finding antibiotic-producing bacteria within our own bodies.

“The reason we ran out of antibiotics in the first place is because most of them came from soil bacteria and they make up 1 percent of the total [bacterial] diversity,” Lewis says.

Scientists kept searching in soil, he says, because they already had some success there and know that soil bacteria are exceptionally good at producing antibiotics.

But now it’s time to look within us. And the team in Tübingen has only just begun their hunt.

“We have started a larger screening program and we’re sure there will be many additional antibiotics that can be discovered,” says Peschel.


That New Superbug Was Found in a UTI and That’s Key

BR3GWM bacteria streaked and grows on an agar plate in the lab
BR3GWM bacteria streaked and grows on an agar plate in the lab


THE WOMAN HARBORING E. coli resistant to colistin did not know it, and it’s only luck that we do. Her doctor would have never prescribed that last-resort antibiotic for a routine urinary tract infection—it can cause serious kidney damage. But her doctor did take a urine sample, which ended up at the Walter Reed National Military Medical Center, where researchers had recently started testing for colistin resistance. The test came back positive. Then the came scary headlines about a new superbug in the US.

Superbugs are bacteria with genetic mutations that let them survive humanity’s harshest weapons in germ warfare: antibiotics. The gene behind this E. coli’s colistin resistance is called mcr-1. It first emerged last year when Chinese researchers found it in samples from hospital patients and raw pork. Why pork? Colistin’s serious side effects mean it’s no longer used as a human antibiotic in many countries. But in China, farmers have been adding it by the pound into feed to fatten animals up.

Once epidemiologists knew to look for mcr-1, they found it in Malaysia, England and then the rest of Europe. It was only a matter of time before colistin resistance turned up in the US. On the same day news came out about this woman’s colistin-resistant UTI, the Department of Health and Human Services also announced it found mcr-1 in a sample from a pig intestine.

Colistin is not used in animal feed in the US, so it’s unclear how colistin-resistant bacteria ended up infecting that woman—or that pig. But food and people move freely across borders. And more even seriously, US animal farmers do use other antibiotics—even human ones—on chicken, pigs, and cows. A growing body of research has linked antibiotic use in food animals to drug-resistant bouts of food poisoning from salmonella, campylobacter, and MRSA. Even more interesting is a possible link between antibiotics on meat and urinary tract infections, which science journalist Maryn McKenna has covered extensively. The Food and Drug Administration issued a guidance last year for farms to phase out medically important antibiotics, though only voluntarily.

The Rise of the Drug-Resistant UTI

Urinary tract infections are damn common—annoyingly common if you ask many women. And antibiotic resistant UTIs are on the rise, too: From 2000 to 2010, the number of UTIs resistant to the antibiotic Cipro went from 3 percent to 17.1 percent. Because UTIs afflict so many people, they’re fairly representative antibiotic resistance out there in people community—especially compared to the resistant infections that epidemiologists tend to study most intensely, like ones that kill already sick hospital patients. “UTIs are a good picture of what people are being exposed to on a daily basis” says Amee Manges, an epidemiologist at the University of British Columbia. Case in point: That colistin-resistant bacteria in the woman from Philadelphia.

Manges has spent the past fifteen years studying the link between antibiotic use in meat production, especially poultry, and UTIs. Back when she was working on her doctoral thesis at the University of California, Berkeley, she kept seeing young, otherwise healthy students with UTIs. Originally, she thought she was going to track sexual transmission of the E. coli that caused such infections. With that kind of sporadic sexual transmission, she should have seen many different strains. But when she DNA fingerprinted the bacteria, she found they were all the same strain—the same pattern you’d see from a single source, like if the campus cafeteria gave everyone food poisoning. She was never able to trace those UTI cases back to the original source, but she’s been working on the question ever since.

UTIs are so hard to trace because the infection might not set in until long after a patient first acquired to bacteria. Say a woman eats some undercooked chicken. “The bacteria just hangs out in your intestine for months or possibly years,” says Manges. Then you get risk factor for UTI—sex or a catheter insertion—and that bacteria makes its way from, ahem, the end of your gut to the urethra. But getting people to remember what they ate a week ago is hard. Getting people to remember what they ate a year ago? Hahaha.

The Surveillance Net
Nevertheless, Manges and others have found that strains on meat match strains found in UTIs. Because of the difficulty in tracing UTIs, that evidence is not as ironclad as the evidence for antibiotics use and antibiotic-resistant food poisoning. With routine surveillance of UTIs though, epidemiologists could get a better handle of not only resistant bacteria that come from meat—but also other sources like drinking water or travel or family members being in the hospital. But that surveillance doesn’t happen. “There’s no organized infrastructure to get a good handle about resistance rates across communities,” says Kalpana Gupta, an infectious disease specialist at Boston University.

When patients walk in with UTIs, doctors will often hand out antibiotics without doing a urine culture. Growing the bacteria takes two days—testing for antibiotic-resistance a third—and by that time the patient is usually on the mend already. The fact that the women in Philadelphia got tested was unusual. The fact that her sample was tested against colistin even more so. As Gupta says, “Colistin is not something we would even use to treat UTIs.” (Resistance to another class of antibiotics triggered that extra test in this case.)

The Centers for Disease Control and Prevention is now following up with the woman in Philadelphia to find out she ended up with that colistin-strain of E. coli, which has never been found in the US before. Her infection was fortunately not resistant to all antibiotics. But what makes the colistin-resistance gene mcr-1 so worrisome is that it’s on a small loop of DNA that different bacteria easily swap back and forth. Someday, another bacteria already immune to all other antibiotics will pick up mcr-1, too. It’s only a matter of time.

The wider the surveillance net though, the more quickly we’ll find it.