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Newly Discovered Antibiotic Kills Bugs Without Resistance

Groundbreaking research holds promise for treating chronic infections

For years, the resistance of pathogens to antibiotics has put them one step ahead of researchers, which is causing a public health crisis, according to Professor Kim Lewis of Northeastern University. In the January 7 issue of Nature, Lewis and his colleagues present a newly discovered antibiotic that eliminates pathogens without encountering detectable resistance — a finding that challenges long-held scientific beliefs and holds promise for treating chronic infections, such as tuberculosis (TB) and those caused by methicillin-resistant Staphylococcus aureus (MRSA).

The researchers’ pioneering work to develop a novel method for growing uncultured bacteria led to the discovery of the antibiotic, called teixobactin. Lewis’ laboratory played a key role in analyzing and testing the compound for resistance from pathogens. Lewis said this marks the first discovery of an antibiotic to which resistance by mutations of pathogens have not been identified.

According to the research team, the discovery of teixobactin presents a promising new opportunity to treat chronic infections caused by MSRA, which are highly resistant to antibiotics, as well as TB, which involves a combination of therapies with adverse effects.

The screening of soil microorganisms has produced most antibiotics, but only 1% of them will grow in the lab, and this limited resource was over-mined in the 1960s, Lewis explained. He and his colleagues spent years trying to address this problem by tapping into a new source of antibiotics beyond those created by synthetic means: uncultured bacteria, which make up 99% of all species in external environments.

The researchers developed a novel method for growing uncultured bacteria in their natural environment. Their approach involved the iChip, a miniature device that can isolate and help grow single cells in their natural environment, thereby providing researchers with improved access to uncultured bacteria. The investigators have assembled approximately 50,000 strains of uncultured bacteria and have discovered 25 new antibiotics, of which teixobactin is the latest and most interesting, Lewis said.

Teixobactin was discovered during a routine screening for antimicrobial material. Lewis then tested the compound for the development of resistance 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.

“Our impression is that nature produced a compound that evolved to be free of resistance,” Lewis said. “This challenges the dogma that we’ve operated under that bacteria will always develop resistance. Well, maybe not in this case.”

Dr. Gerard Wright, a professor at McMaster University, examined the team’s work in a separate article published in Nature in concert with the new research paper. In his article, Wright noted that, while it remains to be seen whether other mechanisms for resistance against teixobactin exist in the environment, the team’s work could lead to identifying “other ‘resistance-light’ antibiotics.”

Going forward, Lewis and his colleagues hope to develop teixobactin into a drug.

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

Lewis said the latest research lays new ground to advance his work on treating MRSA and other chronic infections.

Source: Northeastern University; January 7, 2015.

 

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