Broad-spectrum antibiotics can disrupt the delicate balance of hundreds of bacterial species in the gut. When this happens pathogenic bacteria can occupy the newly vacant niches turning the gut’s protective microbiome into a potential source of infection. Many infections throughout the body begin in the gut. Pathogens can form a reservoir there and spread to other organs. For the first time we aim to eliminate this reservoir before an infection develops by removing harmful bacteria from the gut explains Dr. Lisa Osbelt-Block project leader and DZIF scientist currently a postdoc in Till Strowig’s department. Rather than creating new antimicrobial agents which remain essential but inevitably damage parts of the microbiome we are focusing on a microbiome-based strategy.

In laboratory experiments and mouse models the team demonstrated that Klebsiella oxytoca can drive out various intestinal pathogens including Salmonella and Klebsiella pneumoniae. The latter alone causes around 800,000 deaths annually and is becoming increasingly resistant to common antibiotics. K. oxytoca works by competing for the same nutrients as harmful bacteria and by modifying the gut environment to help beneficial microbes recover ultimately restoring microbiome balance.

A major challenge is that we are developing a living biotherapeutic (LBP) explains Prof. Till Strowig head of the HZI department Microbial Immune Regulation where the project called DeKox was initiated. Unlike probiotics which can be sold freely an LBP is classified as a drug and must undergo rigorous clinical testing and regulatory approval. Strowig who also leads research groups in the DZIF areas Healthcare-Associated Infections and Community-Acquired Infections at Mucosal Interfaces as well as coordinates the DZIF bridging topic Microbiome notes that the DZIF FlexFund is enabling the team to identify the most promising candidates for development.

The researchers are also working on manufacturing methods and quality control processes for their product. Ultimately we envision a capsule containing freeze-dried bacteria instead of an antibiotic compound ready for phase one clinical trials says Dr. Lisa Osbelt-Block. In the future such an LBP could be used to treat patients with persistent K. pneumoniae colonization especially those with weakened immune systems.

Clinically, the HZI team is collaborating with the Clinical Microbiome Research group led by DZIF scientist Prof. Maria Vehreschild at the University Hospital of Cologne. Vehreschild an infectious disease expert focuses on developing microbiome-based therapies. Prof. Katharina Schaufler head of the Epidemiology and Ecology of Antimicrobial Resistance department at the HZI’s Helmholtz Institute for One Health (HIOH) is also contributing to the project conducting virulence tests on candidate strains to ensure their safety.

Source: https://www.helmholtz-hzi.de/en/media-center/newsroom/news-detail/fighting-infections-with-the-power-of-the-microbiome/