{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:56:35Z","timestamp":1787496995132,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Macrolide antibiotics are used in treating Pseudomonas aeruginosa chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects of the newly synthesized P. aeruginosa quorum-sensing autoinducer analogs (AIA-1, -2) on the activity of azithromycin and clarithromycin against P. aeruginosa. In the killing assay of planktonic cells, AIA-1 and -2 enhanced the bactericidal ability of macrolides against P. aeruginosa PAO1; however, they did not affect the minimum inhibitory concentrations of macrolides. In addition, AIA-1 and -2 considerably improved the killing activity of azithromycin and clarithromycin in biofilm cells. The results indicated that AIA-1 and -2 could affect antibiotic tolerance. Moreover, the results of hydrocarbon adherence and cell membrane permeability assays suggested that AIA-1 and -2 changed bacterial cell surface hydrophobicity and accelerated the outer membrane permeability of the hydrophobic antibiotics such as azithromycin and clarithromycin. Our study demonstrated that the new combination therapy of macrolides and AIA-1 and -2 may improve the therapeutic efficacy of macrolides in the treatment of chronic P. aeruginosa biofilm infections.<\/jats:p>","DOI":"10.3390\/antibiotics11010010","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Pseudomonas aeruginosa through Antibiotic Tolerance Reduction"],"prefix":"10.3390","volume":"11","author":[{"given":"Mizuki","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"},{"name":"Department of Microbiology and Genetic Analysis, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"},{"name":"Department of Clinical Nutrition, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, Kurashiki 701-0193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hiroshima","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Amoh","sequence":"additional","affiliation":[{"name":"Department of Dental Hygiene, Mejiro University College, Tokyo 161-8539, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayu","family":"Sebe","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, Kurashiki 701-0193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Genetic Analysis, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-4165","authenticated-orcid":false,"given":"Hideki","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial biofilms: A common cause of persistent infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/441300a","article-title":"The superficial life of microbes","volume":"441","author":"Kolter","year":"2006","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.mib.2007.09.010","article-title":"Role of polysaccharides in Pseudomonas aeruginosa biofilm development","volume":"10","author":"Ryder","year":"2007","journal-title":"Curr. 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