Rare Good News On Antibiotic Resistance: Promise Of Tougher New Drug

Here's a rare treat: potential good news about antibiotic resistance.

For years, the drumbeat of warnings has grown increasingly dire: The bugs are evolving more and more resistance to our biggest antibiotic guns. Some bacteria — strains of tuberculosis and gonorrhea among them — have even become resistant to all antibiotics. Remember the bad old days before these wonder drugs, when bacterial infections were so often death sentences? No one wants to go back there.

So today's report in the journal Nature offers a nicely contrasting ray of antimicrobial hope: It reports the discovery in soil of a potentially powerful new antibiotic, dubbed teixobactin (pronounced takes-o-bactin), that appears to be less vulnerable to evolving resistance than other antibiotics.

"Early on, we saw that there was no resistance developed to teixobactin, and this is of course an unusual and intriguing feature of the compound," says Northeastern professor Kim Lewis, senior author on the Nature paper. The methods used to discover and develop the compound have "a good chance of helping revive the field of antibiotic discovery," he says.

Northeastern Prof. Kim Lewis, director of the Antimicrobial Discovery Center in the College of Science, researches novel antibiotic treatments. (Brooks Canaday/Northeastern Univ.)
Northeastern Prof. Kim Lewis, director of the Antimicrobial Discovery Center in the College of Science, researches novel antibiotic treatments. (Brooks Canaday/Northeastern Univ.)

Teixobactin worked "exceptionally well" to kill resistant bacteria in mice, Lewis says, but it will take several years and probably over $100 million to develop it into a drug that could be prescribed to human patients. It's among two dozen other compounds that he and colleagues have turned up using a novel method to develop substances found in soil that could be useful as antibiotics.

Teixobactin works by attacking the biological building blocks of the bacteria's cell walls, says co-author Tanja Schneider of the University of Bonn. That basic target, which is hard for the cell to modify, may help explain why the bacteria seem unable to develop resistance, she says.

Funding for the work came from the government but a company was also involved in the research. Dr. Lewis and Northeastern colleague Slava Epstein co-founded NovoBiotic Pharmaceuticals, LLC, which collaborated on the study and is working on developing the new antibiotics.

Prof. Lewis argues that compounds like teixobactin could lead to a paradigm shift on how to combat antibiotic resistance. "We, myself included, have been operating under the dogma that resistance development is inevitable, and what we need to focus on is introducing new antibiotics faster than pathogens acquire resistance," he says. "Well, teixobactin gives us an example of how we can adopt an alternative strategy and focus our efforts on developing compounds to which resistance is not going to develop."

Other researchers may say that possible paradigm shift is a big "if," because other antibiotics that seemed resistance-proof have eventually developed it. But at the least, the Nature report does seem to portray a compound with unusual promise for long-lasting power against tough bugs.

From Northeastern University press release, some of the nuts and bolts:

The research team says teixobactin’s discovery presents a promising new opportunity to treat chronic infections caused by staphylococcus aureus, or MSRA, that are highly resistant to antibiotics, as well as tuberculosis, which involves a combination of therapies with negative side effects.

The screening of soil microorganisms has produced most antibiotics, but this limited resource was overmined in the 1960s, Lewis explained. He and Epstein spent years seeking to address this problem by tapping into a new source of antibiotics beyond those created by synthetic means: uncultured bacteria, which make up 99 percent of all species in external environments. They developed a novel method for growing uncultured bacteria in their natural environment, which led to the founding of NovoBiotic. Their approach involves the iChip, a miniature device Epstein’s team created that can isolate and help grow single cells in their natural environment and thereby provides researchers with much improved access to uncultured bacteria. NovoBiotic has since assembled about 50,000 strains of uncultured bacteria and discovered 25 new antibiotics, of which teixobactin is the latest and most interesting, Lewis said.

The antibiotic was discovered during a routine screening for antimicrobial material using this method. Lewis then tested the compound for resistance development and did not find mutant MSRA or Mycobacterium tuberculosis resistant to teixobactin, which was found to block several different targets in the cell wall synthesis pathway.

In 2013, Lewis revealed groundbreaking research in a separate paper published by Nature that presented a novel approach to treat and eliminate MRSA—the so-called “superbug” that infects 1 million Americans annually. Lewis and his team discovered a way to destroy the dormant persister cells, which are key to the success of chronic infections caused by MRSA.

The Nature paper is here and further reading: The New York Times' "From A Pile of Dirt, Hope for a Powerful New Antibiotic".

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Carey Goldberg Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth section.



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