Innovative anti-infective therapies
Novel therapeutic approaches, including antibiotic combinations and bacteriophage-based therapies, as well as evolution- and microbiome-based strategies, aim to preserve the effectiveness of existing antibiotics and expand treatment options.
Within the central theme "Innovative anti-infective therapies," we develop novel approaches for the prevention and treatment of infections caused by multidrug-resistant pathogens. As many clinically relevant pathogens colonize humans before causing disease, a major focus is on targeted decolonization strategies and alternatives to conventional antibiotic monotherapy. Infections caused by multidrug-resistant strains that are no longer susceptible to standard antibiotics are of particular concern.
Decolonization using microbiota-based therapeutics
Infections with multidrug-resistant bacteria do not typically arise spontaneously but are the result of a multi-step process. Through our environment and diet—or through contact with healthcare facilities—multidrug-resistant bacteria can colonize the external and internal surfaces of the human body. The gut plays a particularly important role in this process as the body's largest bacterial reservoir. While multidrug-resistant pathogens are initially present only at low abundance, the selective pressure exerted by antibiotic therapy can lead to a substantial expansion of these organisms.
To eliminate colonization with multidrug-resistant pathogens in high-risk patients, for example prior to hospitalization, DZIF researchers are developing microbiota-based therapeutics that build on the extensive microbiome research conducted in recent years.
In clinical and preclinical studies, biotherapeutic products for decolonization are being developed based on fecal microbiota transfer (FMT) as well as selected bacterial strains, including Klebsiella oxytoca, Staphylococcus lugdunensis, and Staphylococcus capitis. These candidates are being further developed for use in clinical trials.
Targeted bacteriophage therapy
An innovative strategy for combating bacteria in a highly targeted manner is the development of bacteriophage cocktails and therapeutic agents derived from bacteriophages. Bacteriophages are viruses that exclusively infect bacteria, are highly specific to particular bacterial species, and do not adversely affect the healthy microbiota. Together with the industry partner ↗ HyPharm, the phage lysin HY-133 is being tested in a clinical trial for nasal application to kill only Staphylococcus aureus while leaving other species in the nose unaffected.
As part of the EVREA-Phage project, DZIF researchers have developed phage candidates as a cocktail for the decolonization of Enterococcus faecium in the gut and successfully tested them in a mini-gut model developed in Bonn. These candidates are being prepared for evaluation in high-risk patients. In addition, bacteriophages and phage lysins have been identified against other pathogens from the ESKAPE group and are currently being further developed for therapeutic use. At the same time, the highly successful collaboration with DZIF PhageNet and the company ↗ Jafral is being strengthened.
Immunotherapies based on monoclonal antibodies
Therapeutic antibodies have revolutionized the treatment of numerous serious diseases. Over the past decade, antibodies have also demonstrated significant potential in the treatment and prevention of infections, such as COVID-19 and HIV. This approach is now being applied to infections caused by the ESKAPE pathogens Pseudomonas aeruginosa and Staphylococcus aureus.
DZIF researchers have isolated highly potent antibodies against Pseudomonas aeruginosa from immune cells of patients with cystic fibrosis. In preclinical animal models, these antibodies proved to be as effective as conventional antibiotics against P. aeruginosa. They are therefore being further developed for therapeutic application within the PANTIPA project.
Pathoblockers
Unlike antibiotics, pathoblockers do not kill bacteria. Instead, they interfere with specific mechanisms that mediate bacterial pathogenicity—that is, the harmful effects bacteria exert on affected organs—thereby reducing disease severity. To provide alternative or adjunctive treatment options, particularly for infections caused by multidrug-resistant pathogens, combined resistance breakers and pathoblockers targeting the ESKAPE pathogen Pseudomonas aeruginosa are being developed in Tübingen.
