Antibiotic-resistant bacteria are a crucial health concern worldwide not only to infected people, but also to our healthcare systems in general. Infections with the bacterium P. aeruginosa in particular are a threat due to numerous resistance mechanisms, often leading to complicated infections of the lungs and dangerous sepsis, especially in severely ill patients. In addition, the pathogen can permanently colonize organs such as the lungs, where it promotes progressive tissue damage. Often, so-called last-resort antibiotics must be used to treat infected patients, as the standard treatments no longer work. New therapeutic approaches are therefore urgently needed to ensure effective treatment for infections with multi-resistant pathogens such as P. aeruginosa in the future.
In their study, the researchers therefore investigated whether the approach of isolating broadly neutralizing human antibodies, which has been successful for viral infections, could also be used for the development of new therapies against bacterial infections. "Many of the therapeutic antibodies that are already being used against viruses have been isolated and developed from infected, recovered or vaccinated individuals," said lead author Dr Alexander Simonis, resident physician at the Infectiology Department of Department I of Internal Medicine and head of the BMBF-funded junior research group 'Immunotherapies against bacterial infections' at the UoC's Center for Molecular Medicine Cologne.
The research team isolated highly effective antibodies against this pathogen from immune cells of patients with cystic fibrosis who were chronically infected with P. aeruginosa. These antibodies block an important virulence factor of the bacterium, the so-called type III secretion system, which plays an important role especially in severe infections with P. aeruginosa. In extensive experiments using cell cultures and animal models, the researchers were able to show that the newly developed antibodies are as effective against the bacterium as conventional antibiotics. However, since the activity of these antibodies is independent of the mechanisms of action and resistance of antibiotics, these so-called pathoblockers can also -- in contrast to many conventional antibiotics -- work on highly resistant bacteria.
