Research into alternatives to antibiotics wins award in the category of basic research
The researchers have developed an antibody that targets the hospital germ Pseudomonas (P.) aeruginosa. P. aeruginosa often causes severe infections and antibiotic resistance. The antibody is an alternative to antibiotics without being an antibiotic in the traditional sense. This is one reason why the Cologne team prevailed over eight nominated research groups, explained Prof. Dr. Thomas Eschenhagen, Galenus juror and director of the Institute of Pharmacology at the University of Hamburg. A total of three groups from the field of antibiotic resistance were nominated this year. Prof. Eschenhagen: “This is no surprise, as antibiotic resistance is one of the major problems in medicine.”
The teams led by Prof. Jan Rybniker, Department of Internal Medicine I and member of the Center for Molecualr Medicine Cologne (CMMC), and Prof. Florian Klein, Institute of Virology and Executive Board Member at the CMMC, have isolated and characterized antibodies from chronically infected patients that target the virulence of the bacterium. The team tested the antibodies in a mouse model. There, they suppressed the growth of the bacteria with similar effectiveness to classic antibiotics and were also effective against resistant strains. The research work convinced the jury because it was particularly innovative and clinically relevant, explained Prof. Eschenhagen: “The group is very actively driving clinical development forward, so we see prospects for relatively rapid application in patients.”
Dr. Alexander Simonis, Pinciple Investigator at the Center for Molecular Medicine Cologne (CMMC), and Prof. Klein from Cologne University Hospital accepted the award in Berlin. They are confident that their research will lay new foundations for combating microbial antibiotic resistance and have demonstrated that there are other therapeutic modalities for treating bacterial pathogens. The findings could potentially be transferred to other bacterial pathogens.
P. aeruginosa is known to cause severe pneumonia and wound infections, among other things. Due to rapidly increasing resistance, the development of antibiotics with a new mechanism of action is essential. The focus is also on bacterial virulence factors, as the risk of resistance development is considered low for therapies that target virulence factors.
The research conducted by the teams led by Prof. Rybniker, Dr. Simonis, Prof. Klein, and PD Dr. Christoph Kreer at the University Hospital of Cologne focuses on the important type III secretion system (T3SS). T3SS can inject bacterial toxins directly into host cells via the PcrV protein. The starting point for the work was the blood plasma of chronically infected individuals, which had high inhibitory activity against PcrV. Specific B cells were isolated from the plasma. Using single-cell analysis, it was then possible to obtain human monoclonal antibodies (mAb) against PcrV. In an in vivo mouse infection model, these mAb reduced the number of bacteria and the damage to lung tissue. Several mAbs were as effective as conventional antibiotics (Cell 2023; 186: 5098-5113). In addition, the mAbs also had a protective effect against highly resistant P. aeruginosa strains.
Initial tissue cross-reactivity studies did not reveal any negative signals - a known advantage of fully human mAbs. Pharmacokinetic studies showed a long half-life for the mAbs, which could also enable prophylactic use. A Phase I clinical trial is currently being prepared.
This message has been modified by the CMMC (K. Heber & D. Grosskopf-Kroiher) and is based on the text by the press and communications teams of the University Hospital Cologne (original German version here).