Antibiotic resistance – a technical solution after all?

Killing bacteria outside of the body is a relatively simple and straightforward process – denature their proteins by heat or chemicals and thereby kill them. The bacteria can’t get resistant since the denaturalisation process is non-selective, targeting all proteins. Such an approach is not possible once the bacteria have colonized the body, however, since it would harm or kill the host. It is therefore necessary to find a (relatively) specific aspect of microbial metabolism and attack that. However, life-forms can continue using alternative pathways for which the anti-microbial selects if used over a long enough period – a living example of evolution. The obvious place to hit a bacterium is the cell wall, since there is no equivalent in mammalian cells, which are surrounded only by a membrane. Bacteria, however, find a way around this solution, producing neutralizing enzymes to destroy the active part of the antibiotic. So what we need is a molecule that attacks the cell wall and which lies outside the range of neutralizing proteins afforded by nature. A recent report suggests that just such a compound may have been discovered.[1] This compound, termed teixobactin, has been discovered in a soil bacterium, Eleftheria terrae, which cannot be cultured by traditional means. This compound is bactericidal against Gram-positive bacteria (such as MRSA, VRSA and C. difficile) and it has proven impossible to generate resistance in the laboratory – at least so far!

Further, the method used to obtain texiobactin may also be able to help us find other bactericidal compounds. Conventional laboratory methods of growing microbes from soil kill off 99%, but the authors followed a different strategy using “isolation cells” that protect the bacterium sample with a semi-permeable membrane and allow it to grow in its natural environment prior to plating. This method could potentially allow us to recover 50% of soil bacteria, and hence potentially identify many more new antibiotics.

— Richard Lilford, CLAHRC WM Director
— Peter Chilton, Research Fellow

Reference:

  1. Ling LL, Schneider T, Peoples AJ, et al. A new antibiotic kills pathogens without detectable resistance. Nature. 2015; 517(7535): 455-9.

 

 

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