{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:27:03Z","timestamp":1783819623717,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fungal implant\u2010associated bone infections are rare but difficult to treat and often associated with a poor outcome for patients. <jats:italic>Candida<\/jats:italic> species account for approximately 90% of all fungal infections. In vivo biofilm models play a major role to study biofilm development and potential new treatment options; however, there are only a very few in vivo models to study fungi\u2010associated biofilms. Furthermore, mammalian infection models are replaced more and more due to ethical restrictions with other alternative models in basic research. Recently, we developed an insect infection model with <jats:italic>Galleria mellonella<\/jats:italic> larvae to study biofilm\u2010associated infections with bacteria. Here, we further expanded the <jats:italic>G. mellonella<\/jats:italic> model to study in vivo fungal infections using <jats:italic>Candida albicans<\/jats:italic> and <jats:italic>Candida krusei<\/jats:italic>. We established a planktonic and biofilm\u2010implant model to test different antifungal medication with amphotericin B, fluconazole, and voriconazole against the two species and assessed the fungal biofilm\u2010load on the implant surface. Planktonic infection with <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. krusei<\/jats:italic> showed the killing of the <jats:italic>G. mellonella<\/jats:italic> larvae at 5\u2009\u00d7\u200910<jats:sup>5<\/jats:sup>\u2009colony forming units (CFU). Treatment of larvae with antifungal compounds with amphotericin B and fluconazole showed significant survival improvement against planktonic <jats:italic>C. albicans<\/jats:italic> infection, but voriconazole had no effect. Titanium and stainless steel K\u2010wires were preincubated with <jats:italic>C. albicans<\/jats:italic> and implanted inside the larvae to induce biofilm infection on the implant surface. The survival analysis revealed significantly reduced survival of the larvae with <jats:italic>Candida<\/jats:italic> spp. infection compared to noninfected implants. The treatment with antifungal amphotericin B and fluconazole resulted in a slight and nonsignificant improvement survival of the larvae. The treatment with the antifungal compounds in the biofilm\u2010infection model was not as effective as in the planktonic infection model, which highlights the resistance of fungal biofilms to antifungal compounds like in bacterial biofilms. Scanning electron microscopy (SEM) analysis revealed the formation of a fungal biofilm with hyphae and spores associated with larvae tissue on the implant surface. Thus, our study highlights the use of <jats:italic>G. mellonella<\/jats:italic> larvae as alternative in vivo model to study biofilm\u2010associated implant fungal infections and that fungal biofilms exhibit high resistance profiles comparable to bacterial biofilms. The model can be used in the future to test antifungal treatment options for fungal biofilm infections.<\/jats:p>","DOI":"10.1002\/jor.25572","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T02:49:13Z","timestamp":1682045353000},"page":"2547-2559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>Galleria mellonella<\/i> as an alternative in vivo model to study implant\u2010associated fungal infections"],"prefix":"10.1002","volume":"41","author":[{"given":"Gopala K.","family":"Mannala","sequence":"first","affiliation":[{"name":"Department of Trauma Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Rupp","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nike","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin J.","family":"Scholz","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Simon","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Hygiene University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-3179","authenticated-orcid":false,"given":"Martijn","family":"Riool","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0208-4650","authenticated-orcid":false,"given":"Volker","family":"Alt","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery University Hospital Regensburg  Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ma12030495"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040181"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/biom.22905"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10040458"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-091014-104330"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.26"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110550"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftw018"},{"issue":"95","key":"e_1_2_9_10_1","article-title":"Candida albicans biofilm development on medically\u2010relevant foreign bodies in a mouse subcutaneous model followed by bioluminescence imaging","author":"Kuchar\u00edkov\u00e1 S","year":"2015","journal-title":"J Vis Exp"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics4010001"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/845352"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.026294-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00480-10"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00697-10"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13693780701644140"},{"key":"e_1_2_9_17_1","volume-title":"The principles of humane experimental technique","author":"William R","year":"1959"},{"issue":"5","key":"e_1_2_9_18_1","first-page":"505","article-title":"Whole\u2010genome comparison of high and low virulent Staphylococcus aureus isolates inducing implant\u2010associated bone infections","volume":"308","author":"Mannala GK","year":"2018","journal-title":"IJMM"},{"issue":"8","key":"e_1_2_9_19_1","first-page":"1","article-title":"Listeria monocytogenes induces a virulence\u2010dependent microRNA signature that regulates the immune response in galleria mellonella. 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