Entwicklung und Charakterisierung eines trojanischen Helicobacter pylori
Abstract
The human pathogen Helicobacter pylori is a bacterium that colonizes the human stomach and is involved in the development of stomach ulcers and cancer. More than half of the world's population is already infected with H. pylori. The pathogen is well adapted to the environment in the stomach and different courses of disease can be observed depending on various individual factors such as microbiome and immune status. Current therapies rely solely on antibiotics. However, resistance to therapy-relevant antibiotics makes it difficult to treat patients effectively, which is why alternative antibiotic-free therapy approaches are needed in the long term to supplement or replace antibiotics, such as with antimicrobial peptides (AMPs). To enable effective antibiotic-free eradication of H. pylori in the future, the efficacy of 13 AMPs against H. pylori was investigated. The peptides LL-37 and Nisin A were found to be the most effective candidates. By recording dose-response curves, an almost similar mean inhibitory concentration (IC50) in the lower micromolar concentration range was determined for LL-37 (~12 µM) and Nisin A (~11 µM). Furthermore, all AMPs were analyzed with regard to their cytotoxic and hemolytic activity as well as their sensitivity to the digestive enzyme pepsin present in the human stomach. To deliver the drug to the site of infection, a modified H. pylori strain was to be developed that can act as a Trojan horse and colonize in the immediate vicinity of the…
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