{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:37:11Z","timestamp":1787733431099,"version":"build-2784847793"},"reference-count":85,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives: Pseudomonas aeruginosa is an opportunistic pathogen of high clinical relevance due to its ability to form biofilms, its inherent virulence regulated by quorum-sensing systems, and its multidrug resistance. In the present study, we evaluated the inhibitory potential of nine extracts from Inula species (chloroform and methanolic fractions, including a sesquiterpene lactone-enriched fraction) against biofilm formation and virulence-associated traits of P. aeruginosa PAO1 and three multidrug-resistant clinical isolates, as well as their cytotoxicity, biocompatibility, and ability to affect cytokine and nitric oxide production in infected skin explants. Methods: The following methods were applied: fractionation and extraction of plant extracts; cytotoxicity assessment on HFF cells; crystal violet assay for determining antibiofilm activity; fluorescence microscopy for evaluating biofilm viability; electron microscopy for assessing the 3D structure of biofilms and morphological alterations; inhibition assays of pyocyanin pigment, protease activity, bacterial motility, interleukin-17, and nitric oxide production; histological analysis of mouse skin explants. Results: Quantitative analyses of antibiofilm activity revealed that five of the tested extracts inhibited biofilm formation by more than 50%. Structural and functional analyses using confocal laser scanning microscopy and scanning electron microscopy demonstrated a substantial reduction in biofilm thickness, exfoliation of biofilm biomass, the presence of isolated bacterial clusters, metabolically inactive cell populations, and morphological abnormalities associated with cell elongation, invaginations, and polar deformations as a consequence of treatment. In addition, the plant extracts strongly affected virulence factors regulated by quorum sensing. The methanolic fractions from I. britannica and I. bifrons significantly suppressed pyocyanin synthesis. In contrast, the chloroform fractions from I. helenium and I. spiraeifolia produced the largest inhibition zones in assays for extracellular protease activity. Furthermore, all chloroform extracts suppressed bacterial motility, with the lowest swarming diameter observed for the chloroform and lactone-enriched fractions from I. britannica. The chloroform extracts of I. helenium and I. bifrons, methanolic extracts of I. britannica, and chloroform and methanolic extracts of I. spiraeifolia showed relatively low toxicity to normal diploid human fibroblasts. Methanolic and chloroform fractions from I. britannica disrupted biofilm integrity and reduced IL-17A and nitric oxide production in infected skin explants. Conclusions: All these findings indicate a possible synergistic action of the chemical constituents within the fractions on quorum-sensing regulation, biofilm formation, cellular viability, and modulation of host inflammatory responses.<\/jats:p>","DOI":"10.3390\/ph18121824","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"1824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interference of Pseudomonas aeruginosa Virulence Factors by Different Extracts from Inula Species"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8376-8917","authenticated-orcid":false,"given":"Tsvetelina","family":"Paunova-Krasteva","sequence":"first","affiliation":[{"name":"Department of General Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petya D.","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"Department of General Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2783-6342","authenticated-orcid":false,"given":"Tsvetozara","family":"Damyanova","sequence":"additional","affiliation":[{"name":"Department of General Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1514-3699","authenticated-orcid":false,"given":"Dayana","family":"Borisova","sequence":"additional","affiliation":[{"name":"Department of General Microbiology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7370-2383","authenticated-orcid":false,"given":"Milena","family":"Leseva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7088-8500","authenticated-orcid":false,"given":"Iveta","family":"Uzunova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-3712","authenticated-orcid":false,"given":"Petya A.","family":"Dimitrova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Akad. G. Bonchev Street, Bl. 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9056-0333","authenticated-orcid":false,"given":"Viktoria","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 9, 1113 Sofia, Bulgaria"},{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5273-176X","authenticated-orcid":false,"given":"Antoaneta","family":"Trendafilova","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 9, 1113 Sofia, Bulgaria"},{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralitsa","family":"Veleva","sequence":"additional","affiliation":[{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"},{"name":"Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1575-0790","authenticated-orcid":false,"given":"Tanya","family":"Topouzova-Hristova","sequence":"additional","affiliation":[{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"},{"name":"Faculty of Biology, Sofia University \u201cSt. Kliment Ohridski\u201d, 8 Dragan Tsankov Blvd., 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1099\/mic.0.000155","article-title":"Phenotypic Characterization of an International Pseudomonas Aeruginosa Reference Panel: Strains of Cystic Fibrosis (CF) Origin Show Less in Vivo Virulence than Non-CF Strains","volume":"161","author":"Cullen","year":"2015","journal-title":"Microbiology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Damyanova, T., Dimitrova, P.D., Borisova, D., Topouzova-Hristova, T., Haladjova, E., and Paunova-Krasteva, T. 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