The ‘Subterranean Hotel’ for Resistance-Free Antibiotics

A team of researchers recently discovered teixobactin, a candidate antibacterial that has shown good promise against multidrug-resistant bacteria both in cell cultures and laboratory mice.

Many of our important early antibacterial drugs, including tetracycline, streptomycin, and vancomycin, were isolated from soil bacteria, but such discoveries could have only been made serendipitously due to inherent difficulties in cultivating soil bacteria in laboratory environments. However, the researchers involved in this study were aided by the iChip, a cutting-edge microfluidic device which provided the necessary scaffolding for the controlled cultivation of soil bacteria colonies by maintaining their contact with their nutritious soil habitat. The antibiotic produced through this method, teixobactin, is, according to the lead scientist, Professor Kim Lewis, ‘an antibiotic that essentially evolved to be free of resistance.’

Most antibacterials that we commonly deploy attack bacteria through large-molecule targets such as enzymes or proteins using complex, specific mechanisms, which bacteria can relatively easily disrupt by mutating one of the many functional groups involved or creating “dummy targets” that disable the drugs. Teixobactin, on the other hand binds to the small-molecule components Lipids II and III, rendering them unusable for bacteria to build and maintain their cell walls with. Even notoriously drug-resistant bacteria such as MRSA and MDR-TB failed to develop resistance against it in experiments to induce drug resistance, likely because its target molecular segments are so essential to the lipids’ functionality that they cannot be easily modified by the bacteria.

To add to the good news, eleftheria terrae, having an extra membrane layer outside of its cell wall, does not contain genetic parts that confer resistance against teixobactin which other bacteria may utilise. Experts believe however that teixobactin is just the tip of the iceberg – when the iChip gets widespread recognition and usage, we may very well be seeing many more naturally-derived antibacterial designs and entering another Golden Age of antibacterial discovery.

Source: http://dx.doi.org/10.1038/nature14098