The screening of soil bacteria—the approach that has yielded most antibiotics—has been less and less successful, even though its rationale remains sound. Soil microbes locked in mortal combat with each other must secrete substances that keep each other in check. The problem is, few soil microbes, roughly 1%, are amenable to conventional culture techniques, and so a potentially rich source of new antibiotics remains out of reach. Alternative approaches, such as synthetic techniques, have also disappointed.
By revisiting the screening approach—but using a novel method for growing culture-shy bacteria—researchers based at Northeastern University have expanded the search for new antibiotics, dearly needed now that existing antibiotics are increasingly ineffective, due to the rise of antibiotic-resistant superbugs. The researchers, led by Kim Lewis, Ph.D., director of Northeastern’s Antimicrobial Discovery Center, announced that they discovered a new antibiotic, called teixobactin, that cleared up severe infections in mice. Teixobactin caused no side effects and, even better, appeared to deny pathogens easy recourse to resistance.
These promising results appeared January 6 in Nature, in an article entitled, “A new antibiotic kills pathogens without detectable resistance.”
“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),” wrote the authors. “We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin.”
The article also described how the researchers developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. According to a Northeastern University press release, the researchers’ approach involves the iChip, a miniature device that can isolate and help grow single cells in their natural environment.
The iChip, say the researchers, provides them with much improved access to uncultured bacteria. It has already been used to assemble about 50,000 strains of uncultured bacteria and to discover 25 new antibiotics, of which teixobactin is the latest and most interesting. Unlike many of the other newly discovered compounds, it is soluble and so far evidences low toxicity.
“Our impression is that nature produced a compound that evolved to be free of resistance,” Dr. Lewis said. “This challenges the dogma that we’ve operated under that bacteria will always develop resistance. Well, maybe not in this case.”