Thursday, January 08, 2015

A new antibiotic kills pathogens without detectable resistance

Nature published: A new antibiotic kills pathogens without detectable resistance. Here's the abstract:

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.

Kelly Service explains a little more in Science, Microbe found in grassy field contains powerful antibiotic.

Many existing antibiotics, including penicillin, were identified by cultivating naturally occurring microorganisms—bacteria often try to kill each other with chemical warfare, it turns out. But the supply of novel microbes that will grow in a lab has been largely tapped out. In 2002, microbiologist Kim Lewis, along with his colleague at Northeastern University in Boston, microbial ecologist Slava Epstein, described a new technique for coaxing bacteria to grow: Put soil samples into tiny chambers sandwiched between permeable membranes and return these contraptions to the ground. The bacterial strains confined in the chambers will form colonies—thanks in part, the team suspects, to growth factors from neighboring organisms that cross the membranes. The resulting “domesticated” colony can then be removed from the chamber and sometimes will more readily call a petri dish home.

The researchers used a version of this approach to isolate and grow new bacterial colonies—many scooped out of soil in the backyard of microbiologist Losee Ling, who leads research and development at the startup company NovoBiotic Pharmaceuticals, formed to commercialize their approach. To test the antibacterial properties of these soil microbes, the team let each of them duel in a lab dish with Staphylococcus aureus, a cause of serious skin and respiratory infections. Then they isolated and tested individual compounds—10,000 in all—from the bacteria that most effectively killed the staph bacteria.

One bacterium, from a grassy field in Maine, produced a compound with powerful abilities to kill a variety of other bacterial species, including many human pathogens. Moreover, these pathogens failed to develop resistance to the compound: There were no surviving individuals that had evolved to withstand its attack. (Resistance usually develops when a small percentage of microbes escape an antibiotic because of a mutation and then those bacteria multiply.) Lewis initially took this total devastation as a discouraging sign—the mark of “another boring detergent.” (Bleach, after all, is a strong antibiotic, but it’s a little too effective at killing any surrounding cells.) However, it turned out that the new compound, which the group named teixobactin, was not toxic to human cells in a dish.

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