{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:59Z","timestamp":1785301259704,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP24K09808 (S.N.) and JP24K09787 (K.O.)."],"award-info":[{"award-number":["JP24K09808 (S.N.) and JP24K09787 (K.O.)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>In postmortem Alzheimer\u2019s disease (AD) brains, Porphyromonas gingivalis (Pg), a major periodontal pathogen, and Candida albicans, one of the most common fungal pathogens, have been detected. Although it is important to better understand the effects of their co-infection in the brain for elucidating the pathogenesis of AD, little is known about the neuropathological significance of such co-infection. In the present study, we aimed to elucidate the effects of co-exposure to virulence factors derived from Pg and C. albicans on microglial inflammatory responses. We demonstrated, for the first time, that both candidalysin dissolved in dimethyl sulfoxide (CLd) and water (CLw) significantly suppressed Pg lipopolysaccharide (LPS)-induced interleukin-1\u03b2 (IL-1\u03b2) production by 35\u201360% and nuclear factor-\u03baB (NF-\u03baB) activation by 20\u201340%. It should be noted that contaminating Pg outer membrane lipoproteins in Pg LPS were mainly responsible for IL-1\u03b2 production. To examine the possible hydrophobic interactions between lipoproteins contaminating the Pg LPS preparation and CL, we used 8-anilino-1-naphthalenesulfonic acid sodium salt (ANS-Na), which can be excited to emit fluorescence by binding of hydrophobic molecules. The mean fluorescence intensity of ANS-Na was significantly reduced by approximately 26% following co-treatment with CLw and Pg LPS compared with CLw alone. Furthermore, we generated a mutant form of CL with reduced hydrophobicity (GRAVY index: 1.106 vs. 0.874) while preserving its predicted structural properties. This mutant CLd no longer inhibited Pg LPS-induced IL-1\u03b2 production. Taken together, these findings indicate that hydrophobic interactions between lipoproteins contaminating the Pg LPS preparation and CL mediate the inhibitory effect of CL on Pg LPS-induced inflammatory responses. The present findings suggest that interactions between polymicrobial virulence factors in the brain may modulate microglia-mediated inflammatory responses during AD progression.<\/jats:p>","DOI":"10.3390\/ijms27156614","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Candidalysin Inhibits Porphyromonas gingivalis Lipoprotein-Induced IL-1\u03b2 Production in BV-2 Microglia via Hydrophobic Microbial Interactions"],"prefix":"10.3390","volume":"27","author":[{"given":"Haruka","family":"Kanagawa","sequence":"first","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Kawahara","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nene","family":"Mikawa","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Sugihara","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momoha","family":"Ueda","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Nitta","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Egi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Oda","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Nonaka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pathobiology, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Mie 513-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0423-2143","authenticated-orcid":false,"given":"Hidetoshi","family":"Tozaki-Saitoh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka 831-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-548X","authenticated-orcid":false,"given":"Kosuke","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapeutics, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima 729-0292, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2610-3203","authenticated-orcid":false,"given":"Hiroshi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Yasuda Women\u2019s University, Hiroshima 731-0153, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.jalz.2011.04.006","article-title":"Serum antibodies to periodontal pathogens are a risk factor for Alzheimer\u2019s disease","volume":"8","author":"Steffen","year":"2012","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"665","DOI":"10.3233\/JAD-121918","article-title":"Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer\u2019s disease brain tissue","volume":"36","author":"Poole","year":"2013","journal-title":"J. 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