{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:03:40Z","timestamp":1777935820695,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T00:00:00Z","timestamp":1491523200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Industrial Research Fund of KU Leuven","award":["IOF\/KP\/11\/007"],"award-info":[{"award-number":["IOF\/KP\/11\/007"]}]},{"name":"- Flanders FWO","award":["G.0471.12N, G0B2515N"],"award-info":[{"award-number":["G.0471.12N, G0B2515N"]}]},{"name":"Interuniversity Attraction Poles Program initiated by the Belgian Science Policy Office"},{"name":"Industrial Research Fund","award":["IOFm\/05\/022, KU Leuven"],"award-info":[{"award-number":["IOFm\/05\/022, KU Leuven"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Exp Dental Res"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Porphyromonas gingivalis<\/jats:italic> is a major pathogen involved in oral diseases such as periodontitis and peri\u2010implantitis. Management of these diseases typically includes mechanical debridement of the colonized surfaces followed by application of antiseptics or antibiotics. Disadvantages associated with the use of antiseptics and the growing worldwide problem of antibiotic resistance have necessitated the search for alternative agents. In this study, the antibacterial and antibiofilm properties of AM404, an active metabolite of paracetamol, were tested against <jats:italic>P<\/jats:italic>.\u00a0<jats:italic>gingivalis<\/jats:italic> and other bacterial pathogens. The activity of AM404 was tested against 10 bacteria, including both oral and nonoral human pathogens. The minimal inhibitory concentration (MIC) of AM404 was determined by measuring optical density (OD) values. The minimum biofilm inhibitory concentration (MBIC) was detected by crystal violet staining. The activity of structural analogs of AM404 was tested by MIC determinations. The effect of AM404 on <jats:italic>P<\/jats:italic>.\u00a0<jats:italic>gingivalis<\/jats:italic> biofilms formed on titanium disks as a model for dental implants was evaluated by colony forming unit counting. Potential cytotoxicity of AM404 towards HEK\u2010293 (human embryonic kidney cells), HepG2 (human hepatoma cells), IEC\u20106 (rat intestinal cells), and Panc\u20101 cells (pancreatic cancer cells) was assessed by 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide assays. To get more insight in the mode of action of AM404, we used the fluorescent dyes N\u2010phenyl\u20101\u2010napthylamine and SYTOX green to investigate outer and inner membrane damage of <jats:italic>P<\/jats:italic>.\u00a0<jats:italic>gingivalis<\/jats:italic> induced by AM404, respectively. Of all tested pathogens, AM404 only inhibited growth and biofilm formation of <jats:italic>P<\/jats:italic>.\u00a0<jats:italic>gingivalis<\/jats:italic>. Moreover, it showed potent activity against <jats:italic>P<\/jats:italic>.\u00a0<jats:italic>gingivalis<\/jats:italic> biofilms formed on titanium surfaces. A structure\u2013activity analysis demonstrated that the unsaturated carbon chain is essential for its antibacterial activity. Importantly, AM404 was not toxic towards the tested mammalian cells up to concentrations approaching 4\u00d7 the MIC. Membrane damage assays using fluorescent probes N\u2010phenyl\u20101\u2010napthylamine and SYTOX green revealed that membrane permeabilization presumably is the primary antibacterial mode of action of AM404. Collectively, our results suggest that AM404 has the potential to be used for the development of new drugs specifically targeting <jats:italic>P.\u00a0gingivalis<\/jats:italic>\u2010related infections.<\/jats:p>","DOI":"10.1002\/cre2.65","type":"journal-article","created":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T11:48:45Z","timestamp":1491565725000},"page":"69-76","source":"Crossref","is-referenced-by-count":10,"title":["Repurposing AM404 for the treatment of oral infections by <scp><i>Porphyromonas gingivalis<\/i><\/scp>"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2955-829X","authenticated-orcid":false,"given":"Evelien","family":"Gerits","sequence":"first","affiliation":[{"name":"Department of Microbial and Molecular Systems KU Leuven, Centre of Microbial and Plant Genetics  Leuven 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