Richard Honour

Richard Honour

Mar 24, 2015

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Back to the Future - and Back

There are reasons for reviewing older science: They seem to have known what they were doing. The unculturables are still a good idea.

A new antibiotic kills pathogens without detectable resistance

Losee L. Ling, et al. 22 January 2015, Vol 517, Nature, 455, doi:10.1038/nature14098

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.

Widespread introduction of antibiotics in the 1940s, beginning with penicillin and streptomycin, transformed medicine, providing effective cures for the most prevalent diseases of the time. Resistance development limits the useful lifespan of antibiotics and results in the requirement for a constant introduction of new compounds. However, antimicrobial drug discovery is uniquely difficult, primarily due to poor penetration of compounds into bacterial cells. Natural products evolved to breach the penetration barriers of target bacteria, and most antibiotics introduced into the clinic were discovered by screening cultivable soil microorganisms. Overmining of this limited resource by the 1960s brought an end to the initial era of antibiotic discovery.

New organisms, such as uncultured bacteria, are likely to harbour new antimicrobials. This is consistent with resistance mechanisms in soil bacteria being stratified by phylogeny, with horizontal transmission limited (as compared to pathogens) and the pattern of antibiotic production correlating with resistance.

  • Fleming, A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br. J. Exp. Pathol. 10, 226–236 (1929).
  • Schatz, A., Bugie, E. & Waksman, S. A. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc. Soc. Exp. Biol. Med. 55, 66–69 (1944).

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