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We investigated the potential modes of action of several complex, government\u2011approved herbal preparations in clinical use. Four aqueous HMP extracts, fully profiled by LC\u2011MS, did not inhibit UPEC growth but altered early host\u2011UPEC interactions. A stress\u2011reporter assay revealed specific induction of surface stress in\u202f\n                      <jats:italic>E.\u202fcoli<\/jats:italic>\n                      K-12 strain MG1655 via the BaeS\u2011BaeR two\u2011component system, while osmotic, pH, oxidative, SOS, and other stress pathways remained unchanged. This surface\u2011stress response impaired type\u202f1 fimbriae expression and function, markedly decreasing adhesion of UPEC strain\u202fCFT073 to human T24 bladder cells and also lowering intracellular bacterial counts. The extracts did not negatively affect bacterial biofilm formation. To prove these\n                      <jats:italic>in vitro<\/jats:italic>\n                      effects in a more complex model, the HMP extracts were orally fed to\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      larvae to investigate their impact on innate immunity and cellular host response. Oral feeding to uninfected larvae increased innate\u2011immunity gene (moricin, hemolin) expression in the midgut and in circulating hemocytes and markedly increased survival after UPEC infection. The HMP also caused an upregulation of the expression of innate\u2011immunity genes (IL\u20116, IL\u20118, and CXCL\u20113) in uninfected human bladder epithelial cells, indicating an enhanced anti\u2011infective host response. These findings show that HMP can both lower uroepithelial susceptibility to UPEC, by impairing bacterial adhesion and invasion, and enhance host innate defenses. Consequently, such multi\u2011component herbal mixtures represent a promising alternative or complement to antibiotic therapy for UPEC infections through a dual\u2011target mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Traditional herbal medicinal products (HMP) against urinary tract infections protect host cells from uropathogenic E. coli attack.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Some HMP reduce UPEC adhesion to and invasion into bladder epithelial cells.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Some HMP are immunostimulatory and reduce host cell susceptibility to infection.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-026-13794-1","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T23:12:04Z","timestamp":1774307524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Traditional plant urologicals curb early uropathogenic E. coli infection and strengthen host innate defense"],"prefix":"10.1007","volume":"110","author":[{"given":"Madhubani","family":"Dey","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9396-4382","authenticated-orcid":false,"given":"Steffen","family":"Boertz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3470-9117","authenticated-orcid":false,"given":"Krishnendu","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6480-1494","authenticated-orcid":false,"given":"Michael","family":"Berger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-699X","authenticated-orcid":false,"given":"Jandirk","family":"Sendker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Putze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Hensel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9949-1898","authenticated-orcid":false,"given":"Ulrich","family":"Dobrindt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"13794_CR1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00327-18","author":"CE Armbruster","year":"2018","unstructured":"Armbruster CE, Smith SN, Mody L, Mobley HLT (2018) Urine cytokine and chemokine levels predict urinary tract infection severity independent of uropathogen, urine bacterial burden, host genetics, and host age. 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