New weapons against bacterial adhesion, invasion, quorum sensing, cell damaging facors of pathogens: natural products as new anti-virulence compounds

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 Lewis^b 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.

• References

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• 2 Grube K, Spiegler V, Hensel A. Antiadhesive phtalides from Apium graveolens fruits against uropathogenic E. coli. J Ethnopharmacol 2019; 237: 300-306.
• 3 Thöle C, Brandt S, Ahmed N. et al. Aceyted rhanogalacturonans from immature fruits of Abelmoschus esculentus inhibit the adhesion of Helicobacter pylori to human gastric cells by interaction with outer membrane proteins. Molecules 2015; 20: 16770-16787.
• 4 Beydokthi SS, Sendker J, Brandt S. et al. Traditionally used medicinal plants against uncomplicate urinary tract infections: Hexadecy coumaric acid ester from the rhizomes of Agropyron repens (L.) P. Beauv. antiadhesive activity against E. coli . Fitoterapia 2017; 117: 22-27.
• 5 Schmuch J, Becker S, Brandt S. et al. Extract from Rumex acetosa L. for prophyxis of periodontitis: Inhibition of bacterl in vitro adhesion and of gingipains of Porphyromonas gingivalis by epicatechin-3-O-(4β-8)-epiaechin-3-O-galate (procyanidin-B2-di-gallate). PLOSONE(110130): e01201340.