Researchers at the University of Graz are developing modified peptides that are intended to render resistant bacteria harmless extremely quickly and precisely. The substances are based on the body's own defense agents and could represent a promising alternative to conventional antibiotics. Initial results from a project funded by the Austrian Science Fund FWF are encouraging. The study was presented on March 23, 2026, in the science magazine Scilog.
Antibiotic-resistant germs are among the greatest threats in modern healthcare systems. Especially in hospitals, infections after routine procedures such as hip surgery can quickly lead to complications that are difficult to treat, up to life-threatening sepsis. In septic shock, the chance of survival decreases by about eight percent per hour of untreated infection.
Nermina Malanovic from the Institute of Molecular Biosciences at the University of Graz is focusing on antimicrobial peptides, which are part of innate immunity. These small protein structures destroy invading pathogens on the skin and mucous membranes. In the current FWF project "Best-in-Class Novel Antimicrobial and Antiseptic Peptide" (2023–2027, funding amount €399,000), such peptides are being specifically modified to make them suitable for use in the bloodstream.
The active ingredients are based on the human cathelicidin LL-37 and a shortened variant called OP-145 with 24 amino acids. Through targeted changes in the amino acid sequence and helical structure, the peptides electrostatically adhere to the negatively charged membranes of bacteria. Within minutes, they drill holes in the cell membrane, allowing cell contents to escape and killing the pathogen – faster than resistance can develop.
A crucial advantage: the modified peptides are highly selective and hardly attack human cells. Furthermore, they bind to bacterial inflammatory triggers such as lipopolysaccharides (LPS) and lipoteichoic acids (LTA), mask them, and thus prevent an overshooting immune response that leads to life-threatening circulatory failure in sepsis.
Previous work had shown that natural peptides were often too unspecific or were quickly bound in the blood. The current variants show significantly improved properties in laboratory tests regarding selectivity, stability, and anti-inflammatory effects.
Malanovic and her team are now working on further optimizing the molecules and building specialized research infrastructure, including suitable animal models for peptide testing. Regulatory hurdles and raising awareness among the pharmaceutical industry and investors remain challenges. The researcher sees enormous potential: In addition to combating resistant germs, optimized peptides could also be used in the future to fight cancer or combat mold in food. A patent for an antimicrobial peptide has already been filed, with another pending for oncology applications.
Nermina Malanovic is a Senior Scientist Group Leader at the Institute of Molecular Biosciences at the University of Graz. She completed her habilitation in early 2026 and has been leading the project since 2023.
