New antibiotic Darobactin- answer to resistant gram-negative bacteria

"Since the 1960s scientists have not succeeded in developing a new class of antibiotics effective against gram-negative bacteria, but this could now be possible with the help of this peptide," said Prof. Till Schäberle from the Institute of Insect Biotechnology at JLU and project leader at the DZIF. His research group is involved in the discovery. The researchers use a screening, a classical approach from natural product research. Thereby the team of Prof. Kim Lewis, Northeastern University in Boston, Massachusetts (USA), tested extracts of bacterial symbionts of insect-pathogenic nematodes to verify the activity against E. coli. Thus, the researchers were able to isolate a peptide that they have called Darobactin.

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Darobactin consists of seven amino acids several of which are linked via unusual ring closures. The substance shows no cell toxicity -- a prerequisite for the use as an antibiotic. "We have already been able to gain insights about how the bacteria synthesize this molecule," said Prof. Schäberle. "Currently we are working in the field of natural product research at the Institute of Insect Biotechnology of the JLU to increase the production of this substance and to generate analogues."

The researchers also determined the site of action of Darobactin. They found that Darobactin binds to the BamA protein, located in the external membrane of gram-negative bacteria. As a result, the establishment of a functional external membrane is disrupted and the bacteria die off. "It is particularly interesting to note that this previously unknown weak point is located on the outside of the bacteria where substances can easily reach it," explains Prof. Schäberle.

Darobactin exhibited an excellent effect in the case of infections with both wild-types, as well as antibiotic-resistant Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae strains. Thus, Darobactin presents a very promising lead substance for the development of a new antibiotic. The urgency of this matter is also emphasised by the fact that the World Health Organisation (WHO) has attributed the necessity of research and development against resistant pathogens the highest priority for human health.

For further reference log on to :

A new antibiotic selectively kills Gram-negative pathogens. Nature, 2019; DOI: 10.1038/s41586-019-1791-1