{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:47:14Z","timestamp":1785422834499,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt Foundation (AvH), Bonn, Germany","doi-asserted-by":"publisher","award":["3.4-CMR-Hub"],"award-info":[{"award-number":["3.4-CMR-Hub"]}],"id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]},{"award":["3.4-CMR-Hub"],"award-info":[{"award-number":["3.4-CMR-Hub"]}],"id":[{"id":"https:\/\/ror.org\/012kf4317","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Rhineland Palatinate Natural Products Research Center at JGU Mainz"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Microbial resistance to antibiotics has become a major global public health problem, threatening the effectiveness of current therapeutic strategies. The present study seeks to investigate natural compounds originating from fungal sources for their ability to interfere with efflux pump-mediated resistance in multidrug-resistant (MDR) bacteria, with the overarching goal of uncovering new candidates for antimicrobial therapeutic development. A chemical investigation of the ethanol extract of Termitomyces clypeatus was carried out to isolate and identify its constituents. Methods: Structural elucidation of the isolated metabolites was achieved through 1D and 2D NMR spectroscopy supported by mass spectrometric data. The crude extract and the purified compounds were then evaluated for their antibacterial activities individually, in the presence of an efflux pump inhibitor, and in combination with three antibiotics, using standardized microdilution assays. Results: Chromatographic separation of the extract yielded eleven known compounds, including three sphingolipids: (9Z,12Z)-N-(1,3,4-trihydroxyoctadecan-2-yl)octadeca-9,12-dienamide (1), 2-hydroxy-N-(1,3,4-trihydroxyoctadecan-2-yl)hexadecanamide (2), and cerebroside B (3); four steroids: ergosterol (4), cerevisterol (5), ergosterol peroxide (6), and 5\u03b1,6\u03b1-epoxy-(22E,24R)-ergosta-8(14),22-diene-3\u03b2,7\u03b1-diol (7); one alkaloid: piperine (8); one carbohydrate: D-mannitol (9); and two phthalates: dimethyl phthalate (10) and bis(2-ethylhexyl) terephthalate (11). GC\u2013MS analysis led to the identification of eight fatty acid derivatives (12\u201319). Sub-fraction A, along with compounds 3, 4, and 8, exhibited moderate antibacterial activity against some tested strains, with MIC values of 64 \u03bcg\/mL. These compounds were identified as substrates of bacterial efflux pumps, and their presence enhanced the antibacterial effects of ciprofloxacin, doxycycline, and amikacin. Conclusions: The findings of the present work indicate that Termitomyces clypeatus contains compounds with potential therapeutic value, as adjuvants that enhance the activity of conventional antibiotics.<\/jats:p>","DOI":"10.3390\/ph19050737","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:05:46Z","timestamp":1778162746000},"page":"737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antibacterial Activity of Extract, Fractions, and Compounds from Termitomyces clypeatus R. Heim (Lyophyllaceae) Against Multidrug-Resistant Bacteria Overexpressing Efflux Pumps"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1101-6044","authenticated-orcid":false,"given":"Jenifer R. N.","family":"Kuete","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0242-9092","authenticated-orcid":false,"given":"Jason B. T.","family":"Kuete","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris","family":"Baier","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9921-8678","authenticated-orcid":false,"given":"Niklas","family":"Ehlenz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simionne L. K.","family":"Tonga","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bienvenu","family":"Tsakem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-9337","authenticated-orcid":false,"given":"Refilwe","family":"Matshitse","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borice T.","family":"Tsafack","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Eckhardt","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beaudelaire K.","family":"Ponou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-4050","authenticated-orcid":false,"given":"Till","family":"Opatz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Johannes Gutenberg University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9on Azefack","family":"Tapondjou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5384-4755","authenticated-orcid":false,"given":"Ilhami","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Eskisehir Technical University, Eskisehir 26470, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-8351","authenticated-orcid":false,"given":"Xavier","family":"Siwe-Noundou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2051-9091","authenticated-orcid":false,"given":"R\u00e9my B.","family":"Teponno","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Dschang, Dschang P.O. Box 67, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijantimicag.2006.08.024","article-title":"Intraventricular or Intrathecal Use of Polymyxins in Patients with Gram-Negative Meningitis: A Systematic Review of the Available Evidence","volume":"29","author":"Falagas","year":"2007","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S11\u2013S19; discussion S64\u2013S73","DOI":"10.1016\/j.ajic.2006.05.220","article-title":"Antimicrobial Resistance in Gram-Positive Bacteria","volume":"34","author":"Rice","year":"2006","journal-title":"Am. J. Infect. Control"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ferraz, M.P. (2024). Antimicrobial Resistance: The Impact from and on Society According to One Health Approach. 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