Newly Discovered 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. But now scientists have discovered a new 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.

image of gloved hand holding petri dish with pathogens

The research, which is making head­lines around the world and receiving applause from the sci­ence com­mu­nity, was pub­lished Wednesday in the journal 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’ lab 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 Uni­ver­sity of Bonn in Ger­many, Novo­Bi­otic Phar­ma­ceu­ti­cals in Cam­bridge, Mass­a­chu­setts, and Selcia Lim­ited in the United Kingdom.

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 only 1 per­cent of them will grow in the lab, 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 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.

“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 Depart­ment of Bio­chem­istry and Bio­med­ical Sci­ences at McMaster Uni­ver­sity 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 byNature 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.

Story Source:

The above story is based on materials provided by Northeastern University. The original article was written by Greg St. Martin. Note: Materials may be edited for content and length.

Journal Reference:

  1. Losee L. Ling, Tanja Schneider, Aaron J. Peoples, Amy L. Spoering, Ina Engels, Brian P. Conlon, Anna Mueller, Till F. Schäberle, Dallas E. Hughes, Slava Epstein, Michael Jones, Linos Lazarides, Victoria A. Steadman, Douglas R. Cohen, Cintia R. Felix, K. Ashley Fetterman, William P. Millett, Anthony G. Nitti, Ashley M. Zullo, Chao Chen, Kim Lewis. A new antibiotic kills pathogens without detectable resistanceNature, 2015; DOI: 10.1038/nature14098

This article first appeared at ScienceDaily

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