New hope for fighting hospital pathogens
It starts innocently enough: a standard hospital procedure, such as hip surgery, goes according to plan. But then problems arise in the course of wound care. Red and swollen tissue indicates an infection. The patient is immediately given antibiotics to kill the germs causing the infection, but the drugs have no effect and the infection starts spreading. This is the start of a race against time. Apparently resistant to antibiotics, the bacteria threaten to cause sepsis – i.e. blood poisoning. Doctors then need to identify the bacterial strain and find a suitable antibiotic that is kept in reserve for such cases. But especially for older and weaker patients it might already be too late. According to studies, the probability of survival dwindles by eight percent per hour when septic shock is not treated.
Antibiotic-resistant bacterial pathogens feature among the greatest dangers in today's healthcare system and there is an urgent need for effective alternatives to currently used drugs. Nermina Malanovic from the Institute of Molecular Biosciences at the University of Graz is working on a particularly promising approach. In a project funded by the Austrian Science Fund FWF, she is focusing on building blocks of the body's own immune system – so-called peptides.
Some of these small protein structures, which figure among the human immune system’s first line of defense, destroy invading pathogens on the skin or in mucous membranes. “We are trying to modify the peptides in such a way that they specifically neutralize bacterial pathogens in the blood,” explains Malanovic. Initial findings reveal the newly developed peptides as having amazing capabilities. They eliminate bacterial pathogens so efficiently that the germs do not have time to adapt and develop resistance. At the same time, they have an anti-inflammatory effect on the body and can prevent sepsis.
Protein against resistant pathogens
Biochemist Nermina Malanovic is researching how peptides can be used. These protein molecules are important in the body's immune defense system and could be an alternative to antibiotics. Not only that, peptide research promises ample treasures, e.g. for cancer therapy.
Good effectiveness, but application fraught with obstacles
Malanovic has been conducting research on peptides for almost 15 years. As a postdoc at the University of Graz, she investigated their biophysical interaction with bacteria as part of a large EU project. At that time her aim was to coat implants for the human body with an antimicrobial layer. But while there were very effective peptide variants, she realized that application always involved problems. Some peptides were not selective enough and attacked not only pathogens but also body cells. Others clung to other substances in the blood, leading to a decrease in the concentration of free active ingredients, thus reducing biological effectiveness.
Despite these obstacles, her research at the time revealed the exact mechanism behind the antibacterial effect of these molecules. “Because of their positive electrostatic charge, the peptides adhere to the negatively charged cell membranes of the bacteria. They have a helix-like structure which they use to drill small holes in this protective shell of the germs – even in those that can no longer be successfully fought by antibiotics,” explains Malanovic. “In this way, the germs’ membrane structure is destroyed and can no longer encapsulate the cell contents. As this process takes place within minutes, it is faster than the multiplication speed of bacteria and thus renders it unlikely for the germs to develop resistance.”
A peptide with promising properties
In the current FWF project, the researcher is seeking promising candidates and closely investigates their interactions. The basis for this research is a human peptide called cathelicidin LL-37, which even in its natural form fights bacteria as part of the immune system. In principle, peptides consist of an arrangement of different amino acids – 37 in this case. From this base, Malanovic and her team have developed a sequence called OP-145, which has 24 amino acids. “Preliminary findings have shown that we are very close to achieving the desired properties in terms of selectivity and behavior in the bloodstream,” she explains.
What is more, the researchers were able to invest the peptides with a second ability besides their antibacterial effect: “They bind to certain fragments of bacteria that are known to trigger inflammation. The peptide bond masks these components, known as lipopolysaccharides (LPS) and lipoteichoic acids (LTA), so that they are not recognized by the immune system.” This prevents an excessive immune response, which in case of sepsis typically leads to a rapidly progressing systemic inflammatory reaction and, thus, to a life-threatening condition.
Creating research infrastructure
Malanovic is now working on further improving the design of a peptide that combines all these effects. She approaches this, for example, by changing the sequence of amino acids in the peptide to modify its properties, or by adjusting the helical shape of the molecule. In addition, there is a need to improve the infrastructure for peptide research: “In relevant drug development, everything is geared toward the pharmaceutical implementation of antibiotics. There is currently no specialized animal model for studying peptides, for example. There is no clear consensus on how results from the laboratory can be transferred to animals,” explains Malanovic. “Also we need to overcome regulatory hurdles and make investors and the pharmaceutical industry aware of peptides as an alternative to antibiotics.”
Fundamentally, however, as Malanovic emphasizes, peptide research promises ample treasures that have yet to be unearthed – and which go far beyond an alternative to antibiotics. Not only has she filed a patent for an antimicrobial peptide, but also for a peptide that can be used in the fight against cancer. “Cancer research is an important field of research, because peptides can also be modified to eliminate harmful bacteria in the cancer environment or even the tumor cells themselves,” explains Malanovic. “But one can also conceive of a number of other applications – including the fight against food mold. You see, the potential is enormous.” It remains to be seen whether the research successes of the working group will also be commercialized in the context of a spin-off company. As a pioneer in her field of research, Malanovic is now laying the foundations for a class of active substances that will enable new and very target-specific therapies.
About the researcher
Nermina Malanovic is a Senior Scientist and Group Leader at the Institute of Molecular Biosciences at the University of Graz, where she acquired her doctorate and also worked as a postdoctoral researcher after taking breaks for maternity leave and research work at the Austrian Academy of Sciences (ÖAW). She completed her venia docendi in early 2026. Set to run from 2023 to 2027, the project “Best-In-Class novel Antimicrobial and Antiseptic peptide” is awarded EUR 399,000 in funding from the Austrian Science Fund FWF.
Publications
Bacterial Cell Fate Under Stress: Lipid Remodeling and Antimicrobial Peptide Attack, in: npj Antimicrobial and Resistance 2026
SAAP-148 Oligomerizes into a Hexamer Forming a Hydrophobic Inner Core, in: ChemBioChem 2025
Bactericidal Activity to Escherichia coli: Different Modes of Action of Two 24-Mer Peptides SAAP-148 and OP-145, Both Derived from Human Cathelicidine LL-37, in: Antibiotics (Basel) 2023
