ABSTRACT
The problem of multidrug-resistant Helicobacter pylori requires new antibiotics development. We have evaluated a potential antibiotics, moenomycin A, which is classified as a phosphoglycolipid antibiotics that targets transglycosylase and is previously thought to be limited in Gram-positive bacteria. Herein, we report the activity of moenomycin A against multidrug-resistant H. pylori and the isolates from patients with different gastrointestinal diseases.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bambermycins/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Enzyme Inhibitors/pharmacology , Glycosyltransferases/antagonists & inhibitors , Helicobacter pylori/drug effects , Stomach Neoplasms/microbiology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Bambermycins/chemical synthesis , Bambermycins/chemistry , Drug Design , Duodenal Ulcer/microbiology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Gastritis/microbiology , Glycosyltransferases/metabolism , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Helicobacter pylori/enzymology , Helicobacter pylori/isolation & purification , Humans , Microbial Sensitivity Tests , Molecular Conformation , Stomach Ulcer/microbiologyABSTRACT
The recognition of bacteria, viruses, fungi, and other microbes is controlled by host immune cells, which are equipped with many innate immunity receptors, such as Toll-like receptors, C-type lectin receptors, and immunoglobulin-like receptors. Our studies indicate that the immune modulating properties of many herbal drugs, for instance, the medicinal fungus Reishi (Ganoderma lucidum) and Cordyceps sinensis, could be attributed to their polysaccharide components. These polysaccharides specifically interact with and activate surface receptors involved in innate immunity. However, due to the complexity of polysaccharides and their various sources from medicinal fungi, quantitative analysis of medicinal polysaccharide extracts with regard to their functions represents a major challenge. To profile carbohydrate-immune receptor interactions, the extracellular domains of 17 receptors were cloned as Fc-fusion proteins, such that their interactions with immobilized polysaccharides could be probed in an enzyme-linked immunosorbent assay. The results show that several innate immune receptors, including Dectin-1, DC-SIGN, Langerin, Kupffer cell receptor, macrophage mannose receptor, TLR2, and TLR4, interact with the polysaccharide extracts from G. lucidum (GLPS). This analysis revealed distinct polysaccharide profiles from different sources of medicinal fungi, and the innate immune receptor-based enzyme-linked immunosorbent assay described here can serve as a high-throughput profiling method for the characterization and quality control of medicinal polysaccharides. It also provides a means to dissect the molecular mechanism of medicinal polysaccharide-induced immunomodulation events.