Teixobactin: A Promising New Antibiotic from Uncultured Bacteria

[Ryan_m_b]

This paper was shown to me today by a colleague:

A new antibiotic kills bacteria without detectable resistance
L, Ling et al (2015) Nature
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14098.html

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.

It's a fascinating paper, not just for the good results that teixobactin seems to have against gram-negative bacteria but also for it's use of the Ichip (reported in this paper from 2010). The Ichip is a system for cultivating so-called uncultivable bacteria. It works by isolating individual bacteria into small cells on a slide, a semi-permeable membrane covers the cells (trapping the bacteria) and the whole thing is placed in soil. The bacteria survive in this environment and can be easily studied. It's reported that the Ichip can culture 50% of the bacterial species placed into it, a huge improvement over the 1% standard methods generate.

It will be interesting to see if teixobactin comes to anything and if how widespread this method becomes in the pursuit of new antibiotics.

 

[berkeman]

Wow, that's great news, and very promising! Thanks Ryan. :-)