Combating uropathogenic E. coli: from natural products to new molecular targets

Urinary tract infections (UTI) are one of the major infections of humans worldwide, in most cases due to uropathogenic E. coli (UPEC). Therapeutic strategies using antibiotoic treatment are in many cases based on short term treatment, resulting in many cases in antibiotic restiance formation. Traditional medicine describes many herbal medicinal products (HMP) for UTI, for which also manyfold HMPC monographs have been published by EMA. Interestingly, not much scientific and clinical information on the underlying mode of action, molecular targets or active ingredients has been reported. Within systematic investigations of some of these HMP this gap of knowledge could be filled. Polymethoxylated flavones from Orthosiphon stamineus have been shown to be strong inhibitrs of the bacterial adhesion to bladder cells (in vitro, ex vivo) by influencing motitiliy and chaperon-usher system of UPEC. Infection studies in mice indicated strongly reduced infection of kidney and bladder after oral treament with standaridized Orthosiphon extract, similar to norfloxacicn. Malonylated damaran triterpenopids from Betula sp. leaves have been shown to act against early UPEC-host cell interaction. Extracts from Vaccinium macrocarpon are strong stimulators of Tamm-Horsfall Protein (THP) in the Henle tubes of the kidney, leading to improved innate immun defence against UPEC, as the highly mannosylated THP interacts with the mannose-binding site of FimH of UPEC. Also extracts from Equisetum arvense stimulate THP secretion in the kideny after 7 days oral intake in humans significantly, leading to strongly reduced pathogen-host cell interaction. Systematic investigations of traditional used HMP on phytochemical and functional in vitro/ex vivo/in vivo level is a valuable tool for identification of lead structures of natural products against new and innovative targets.