{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:08:14Z","timestamp":1788599294656,"version":"build-2803163510"},"reference-count":86,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>With rising multidrug-resistant yeast pathogens, conventional antifungals are becoming less effective, urging the need for adjuvants that enhance their activity at lower doses. This study evaluated the synergistic activity of antimicrobial peptidomimetics (TM8 and RK758) or colistin sulphate in combination with conventional antifungals against Candida albicans, C. tropicalis, C. parapsilosis, Meyerozyma guilliermondii, Nakaseomyces glabratus, Pichia kudriavzevii and Kluyveromyces marxianus, and Candidozyma auris using the checkerboard microdilution test. RK758 was synergistic with fluconazole in 78% of isolates, with the remaining 22% of isolates still showing partial synergy; it showed synergy with amphotericin B in 56% of isolates, and with caspofungin, 78% of isolates exhibited either synergy or partial synergy. TM8 showed synergy with fluconazole in 44% (with partial synergy in another 44%) of isolates, with amphotericin B in 67% of isolates, and with caspofungin in 44% (with partial synergy in another 44%) of isolates. Colistin with fluconazole or caspofungin exhibited synergy or partial synergy in 56% of the isolates. No antagonism was observed in any of the combinations. Additionally, a time-kill assay further demonstrated synergistic activity between fluconazole and TM8 or RK758. The effects of these peptidomimetics on cell membrane integrity were demonstrated in an ergosterol binding assay, supported by SYTOX Green and cellular leakage assays, both indicating a lytic effect. These results suggest that peptidomimetics can synergise with conventional antifungals, offering a potential strategy for combination therapy against yeast infections. The membrane lytic activity of the peptidomimetics likely plays a role in their synergistic interaction with antifungals, thereby enhancing the antimicrobial activities of both compounds at sub-MIC levels.<\/jats:p>","DOI":"10.3390\/jof11050370","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T09:13:38Z","timestamp":1747041218000},"page":"370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Synergistic Activity of Antimicrobial Peptidomimetics or Colistin Sulphate with Conventional Antifungals Against Yeasts of Medical Importance"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3888-7319","authenticated-orcid":false,"given":"Shyam Kumar","family":"Mishra","sequence":"first","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Department of Microbiology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan University, Kathmandu 44600, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Kuppusamy","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"School of Chemistry, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Nguyen","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Doeur","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harleen","family":"Atwal","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0644-6817","authenticated-orcid":false,"given":"Samuel","family":"Attard","sequence":"additional","affiliation":[{"name":"School of Chemistry, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4400-8715","authenticated-orcid":false,"given":"Kristian","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, School of Medicine and School of Engineering, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, School of Medicine and School of Engineering, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar H. H.","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4151-0384","authenticated-orcid":false,"given":"Alex","family":"Hui","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"School of Optometry & Vision Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-6873","authenticated-orcid":false,"given":"Annelise E.","family":"Barron","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, School of Medicine and School of Engineering, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0951-9621","authenticated-orcid":false,"given":"Naresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Chemistry, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-7563","authenticated-orcid":false,"given":"Mark","family":"Willcox","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/viru.22913","article-title":"Candida albicans pathogenicity mechanisms","volume":"4","author":"Mayer","year":"2013","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a019778","DOI":"10.1101\/cshperspect.a019778","article-title":"The Candida pathogenic species complex","volume":"4","author":"Turner","year":"2014","journal-title":"Cold Spring Harb. 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