Antibiotic kills pathogens without resistance

For years, pathogens’ resis­tance to antibi­otics has put them one step ahead of researchers, which is causing a public health crisis, according to Northeastern Uni­v. Dis­tin­guished Pro­f. Kim Lewis. But in new research, Lewis and his col­leagues present a newly dis­cov­ered antibi­otic that elimi­nates pathogens without encoun­tering any detectable resistance—a finding that chal­lenges long-​​held sci­en­tific beliefs and holds great promise for treating chronic infec­tions like tuber­cu­losis and those caused by MRSA.

The research is pub­lished in Nature.

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

Lewis and North­eastern biology pro­fessor Slava Epstein co-​​authored the paper with col­leagues from the Uni­v. of Bonn in Ger­many, Novo­Bi­otic Phar­ma­ceu­ti­cals in Cam­bridge, Mass­., and Selcia Lim­ited in the U.K.

The research team says teixobactin’s dis­covery presents a promising new oppor­tu­nity to treat chronic infec­tions caused by staphy­lo­coccus aureus, or MRSA, 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 only 1% of them will grow in the laboratory, and 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% 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 MRSA 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.”

Gerard Wright, a pro­fessor in the Dept. of Bio­chem­istry and Bio­med­ical Sci­ences at McMaster Uni­v. and who was not involved in this research, exam­ined the team’s work in a sep­a­rate article for Nature published 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.”

“(The researchers’) work offers hope that inno­va­tion and cre­ativity can com­bine to solve the antibi­otics crisis,” Wright wrote.

Going for­ward, the research team hopes to develop teixobactin into a drug.

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.

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

Source: Northeastern Univ.