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Although antibiotics have transformed medicine, the development of resistance has limited their usefulness. A potential source of new antibiotics is the 99% of bacteria that have not been culturable before.
Now, researchers from academia and the pharmaceutical industry have used a multichannel device — the iChip — to simultaneously isolate and grow previously uncultured bacteria. Dilute soil is delivered to this device, such that each channel contains approximately one bacterial cell. The device is then covered with two semipermeable membranes and placed back into the soil, allowing growth in an organism's native environment. Once a colony is produced, growth on artificial media can be attempted.
Extracts from among 10,000 isolates obtained by these methods were tested for antibacterial activity. A molecule that the researchers called teixobactin, extracted from a new species provisionally named Eleftheria terrae, was found to have activity against numerous gram-positive organisms, including drug-resistant strains. Its mechanism of action appears to be inhibition of peptidoglycan synthesis by binding to nonprotein targets, including lipid II. Despite serial passage of Staphylococcus aureus in low concentrations of teixobactin, no resistance was observed. In a mouse model, teixobactin was found to be nontoxic and effective in treating methicillin-resistant S. aureus and Streptococcus pneumoniae infections.
Ling LL et al. A new antibiotic kills pathogens without detectable resistance. Nature 2015 Jan 7; [e-pub ahead of print]. (http://dx.doi.org/10.1038/nature14098)
Comment
This paper, which has received a lot of attention in the press, features three advances. First, previously unculturable bacteria were grown and characterized. Second, products of these organisms were screened, resulting in the identification of a completely novel antimicrobial, teixobactin. Finally, the activity of teixobactin was found not to depend on binding to a protein, making resistance unlikely to develop. As the authors note, additional natural compounds are likely waiting to be discovered.