Newly released antibiotic against gram-negative bacteria in sight
The rapid spread of antimicrobial resistance has become a worldwide problem. According to the World Health Organization (WHO), gram-negative bacteria are especially a growing threat to human health, and an international research team has discovered a new cure for these troublesome germs.
An international research team with the participation of Justus-Liebig-Universität Gießen (JLU) and the German Center for Infection Research (DZIF) has discovered a new compound against gram-negative bacteria, "Darobactin", which targets unknown sites of action.
According to a DZIF statement, more and more bacterial agents of infectious diseases are developing resistance to standard antibiotics on the market. Common hospital germs, such as Escherichia coli and Klebsiella pneumoniae, have become resistant to most – and in some cases all, antibiotics currently available.
What makes these pathogens so vulnerable is their extra outer membrane. This protects the bacteria especially well by preventing many substances from entering the cellular interior. New drugs specifically for treating diseases caused by these so-called gram-negative bacteria.
An international research team with researchers from the University of Giessen has now discovered a new peptide that attacks gram-negative bacteria at a previously unknown site of action. Their results have been published in the journal Nature.
Candidate for a new class of antibiotics
"It has not been possible to develop a new class of antibiotics against gram-negative bacteria since the 1960s, but this may be a candidate for it now," said Prof. Till Schäberle of the Institute of Insect Biotechnology at JLU and Project Manager at DZIF. His new group is involved in a new discovery.
Scientists have used screening, a classic approach to natural matter research. A team of Professor Kim Lewis of Northeastern University in Boston, Massachusetts (USA) tested bacterial symbiont extracts of insect pathogenic nematodes for activity against E. coli. So the researchers were able to extract a peptide they called "darobactin".
As explained in the communication, Darobactin is composed of seven amino acids and exhibits structural peculiarities: Several amino acids are linked by unusual ring pins. The substance has no cellular toxicity – a prerequisite for use as an antibiotic.
"We have already gained insight into how bacteria synthesize this molecule," Schäberle says. "We are now working in the area of natural products research at JLU Insect Biotechnology Institute to increase production of this substance and create analogues."
The researchers also determined the site of action of darobactin and found that darobactin binds to the BamA protein, which is located in the outer membrane of gram-negative bacteria. As a result, the structure of the functional outer membrane is disrupted and the germs die.
"It's particularly interesting that this previously unknown site of attack is out and that substances can easily reach it," Schäberle said.
It works great for infections
Darobactin has been reported to have excellent effect in antibiotic-resistant infections and species of antibiotic-resistant Pseudomonas aeruginosa and antibiotic-resistant Klebsiella pneumoniae. Therefore, darobactin is a promising guide for the development of a new antibiotic.
The urgency of this is demonstrated by the fact that WHO has identified the research and development needs of resistant pathogens as a top priority for human health.
Researchers from the USA (Northeastern University, Boston, Massachusetts, Purdue University, West Lafayette, Indiana, J. Craig Venter Institute, La Jolla, California), Germany (Justus Liebig University Giessen; DZIF Infection Research Center, Giessen-Marburg- Langen, European Molecular Biology Laboratory EMBL, Heidelberg) and Switzerland (University of Basel). (AD)
This article contains general information only and should not be used for diagnosis or treatment alone. It cannot replace a doctor's visit.