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DOI: 10.1055/s-0039-3399719
New weapons against bacterial adhesion, invasion, quorum sensing, cell damaging facors of pathogens: natural products as new anti-virulence compounds
Publikationsverlauf
Publikationsdatum:
20. Dezember 2019 (online)
Due to increasing antibiotic resistance, new antibaterial compounds have to be developed. As most clinically used antibiotics influence either cell wall assembly, protein formation or membrane funtionality, new molecular targets and specific inhibitors should identified. Receptor-mediated recognition between bacteria and host cell leads to adhesion between both partners, which can specifically be blocked by plant-derived natural products. FimH-mediated interaction of uropathogenic E. coli to uroplacin from human bladder cells can inhibited by polymethoxylated flavones (e.g. sinensitin from Orthosiphon stamineus [1], phtalides from Apium graveolens [2]) as shown within in vitro studies and evidenced by in vivo infection experiments. This is also accompanied by inhibition of bacterial quorum sensing. BabA-and LPS-controlled binding of H. pylori to Lewisb antigens of human stomach cells can be blocked by acetylated rhamnogalacturonans [3]. Internalisation of adhering bacteria into the host cells by membrane-fusion can be inhibited by compounds changing membrane-fluidity of the host cells, as shown for hexadecyl coumaric esters [4]. Fimbriae-located host cell destructing proteases, e.g. arginin- and lysin-specific gingipains from Porphyromonas gingivalis, are the main virulence factors responsible for elimination of epithelial cells during active periodontitis. Galloylated dimeric procyanidins from Rumex acetosa interact specifically with Arg-gingipain by binding into the active center of the proteases, leading to inhibition of proteolytic activity. In vivo pilot study in humans, using a 7-day mouthwash with R. acetosa hydroalcoholic extract 0.8%, reduced significantly clinical symptoms [5]. Summarizing, pinpointing new and specific targets for innovative anti-virulence compounds can effectively be driven by screening of plant-derived natural products.
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References
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