Excerpt from “New Antibiotic from Soil Bacteria” by Anna Azvolinsky
That the antibiotic can kill M. tuberclosis “is a major breakthrough because it is virtually certain to be effective for the multi-resistant strains that are now all but impossible to treat,” said Richard Novick, a microbiologist at New York University Langone Medical Center who was not involved in the work.
Although further studies are needed before the antibiotic can be tested in humans, animal efficacy models are often predictive of a drug’s effects in humans, said Gerard Wright, director of the Institute for Infectious Disease Research at McMaster University in Hamilton, Canada, who penned an accompanyingeditorial.
Teixobactin was isolated from a previously unknown Gram-negative bacterium that lives in soil and cannot be cultured in the lab using standard techniques. So the researchers applied an approach called Ichip, developed jointly by Lewis and Slava Epstein’s lab, in which a soil sample is diluted with agar, and a single bacterial cell is suspended in a chamber surrounded with semi-permeable membrane. The researchers pack 96 such chambers into a single device, which they then place in soil—allowing the bacteria access to nutrients and growth factors but not to escape. This cultivation approach is an innovative way to tap into the rich biodiversity that we are currently missing because only 1 percent of microorganisms can be cultured in the lab, said Wright. “This biodiversity is also hiding a lot of chemical diversity that may include other new antibiotics.”
Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.