Scientists in Germany have discovered a new drug to combat one of the most dangerous antibiotic-resistant bacteria in the world, methicillin-resistant Staphylococcus aureus (MRSA), and it’s buried inside human noses. The prospective drug comes from a close relative of MRSA that lives in nasal passages and produces a chemical weapon against its kin.
The results, published today in Nature, open a new path in the fight against drug-resistant bacteria, which experts argue may kill more people than cancer by 2050. The finding marks the first time a human-associated bacteria has yielded a potent antibiotic against a human pathogen.
“We believe that we’ve come up with a new concept,” microbiologist and coauthor Andreas Peschel of the University of Tübingen said in a press conference Tuesday. “It was totally unexpected to find a human-associated bacteria that produces a real antibiotic.”
Though scientists typically search for such antibiotics typically in soil or the environment, Peschel team’s thought the human body seemed a natural place to look. Trillions of microbes make homes on humans, and like with any ecosystem, there’s bound to be competition. Staphylococcus aureus, for example, is found in the nose of every third person, but this prevalence is so high that it’s surprising more people are not infected. “Understanding what brings the bacteria into the noses of certain people but not others” was one of our goals, Peschel said.
So, he and his colleagues screened a group of bacteria species related to MRSA to see if any strains could outcompete their dangerous cousin.
They uncovered one species — Staphylococcus lugdunensis — that eradicated MRSA by producing a compound the researchers dubbed lugdunin (pronounced lug-done-in). In one experiment, mice with MRSA skin infections recovered quickly after treatment with topical lugdunin ointments.
“We saw a dramatic reduction in the bacterial numbers. Some of the animals were completely cleared,” microbiologist and study coauthor Bernhard Krismer said.
Moreover, this drug may already be working in humans. When the team examined 187 hospitalized patients, they learned that S. aureus and S. lugdunensis rarely hang out in the same nose. S. aureus was present in only 5.9 percent of individuals who also carried S. lugdunensis, compared with 34.7 percent in people without S. lugdunensis.
In an op-ed article also published in Nature today, microbiologists Kim Lewis and Philip Strandwitz of Northeastern University in Boston argue that S. lugdunensis may represent just the tip of a new MRSA spear.
“Given that S. lugdunensis is present in only around 10 percent of the population and S. aureus is found in about 30 percent of the population, there are probably more antibiotics yet to be discovered that are responsible for S. aureus colonization resistance,” Lewis and Strandwitz wrote.
Further tests are needed before lugdunin is ready for clinical use as a drug (or before S. lugdunensis is used as a probiotic. The team found that mixing lugdunin with human blood extracts did not reduce its potency, but the compound doesn’t easily dissolve in water, which hurts the ability of engineering the drug on a large scale.
Peschel and Krismer plan to modify lugdunin’s structure to improve its water solubility, but any small tweak may change its ability to stop MRSA. It’s unclear how exactly lugdunin kills MRSA, but the researchers suspect proteins embedded in the bacteria’s outer shells — called membrane transporters — play a role.
“[S. lugdunensis] has membrane transporters which are necessary to export [lugdunin]. If you delete these genes, it kills itself,” Krismer said. “But on the other hand, if you bring these transporters into [MRSA], it doesn’t get resistance.”
This finding also suggests that MRSA couldn’t easily mutate or acquire the machinery needed to build resistance against lugdunin.
“We exposed multiple S. aureus strains to lugdunin, but it seems the microbe has never become resistant,” Peschel said. “For whatever reason, it seems difficult, if not impossible, for S. aureus to become resistant.”