For a long time, antibiotics were considered a silver bullet against bacterial infections. Over time, many pathogens have adapted to resist antibiotics, so the search for new drugs is becoming increasingly important. An international team of researchers, including scientists at the University of Basel, has now discovered a new antibiotic by computational analysis and deciphered its mode of action. Their study is an important step in the development of new effective drugs.

The WHO calls the creeping and rapidly growing number of antibiotic-resistant bacteria a “silent pandemic.” The crisis is aggravated by the fact that hardly any new drugs have come onto the market in recent decades. Even today, not all infections can be treated successfully and patients are at risk from routine interventions.

In order to stop the advance of antibiotic-resistant bacteria, new active substances are urgently needed. Such an important discovery has now been made by the team led by researchers from the Northeastern University in Boston together with Prof. Sebastian Hiller from the Biozentrum of the University of Basel. This study was part of the National Centre of Competence in Research (NCCR) “AntiResist” and has now been published in “Nature Microbiology.”

Tough opponents

The researchers discovered the new antibiotic Dynobactin by a computational screening approach. This compound kills Gram-negative bacteria, which include many dangerous and resistant pathogens. “The search for antibiotics against this group of bacteria is far from trivial,” says Hiller. “They are well protected by their double membrane and therefore offer little opportunity for attack. And in the millions of years of their evolution, the bacteria have found numerous ways to render antibiotics harmless.”

Only last year, Hiller’s team deciphered the mode of action of the recently discovered peptide antibiotic Darobactin. The knowledge gained was integrated into the screening process for new compounds. The researchers made use of the fact that many bacteria produce antibiotic peptides to fight each other. And that these peptides, in contrast to natural substances, are encoded in the bacterial genome.