Antifungal Potential of Streptomyces-Derived Metabolites Against Fluconazole-Resistant Oral Candida albicans: In vitro Evaluation and Mechanistic Insights

Authors
Mahtab Karami-Feli 1
Zahra Jahanshiri 1
Akram Sadeghi 2
1 Department of Mycology, Pasteur Institute of Iran, Tehran, Iran
2 Department of Microbial Biotechnology, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
10.61882/ibj.4937
Abstract
Background: Oropharyngeal candidiasis, primarily caused by Candida albicans, is the most common opportunistic fungal infection in patients with head and neck cancer. The increasing emergence of fluconazole (FLZ) resistance has led to higher morbidity and mortality rates. Streptomyces, a genus of Actinomycetes, produces bioactive molecules with antimicrobial effects. This study investigated the antifungal potential of S. monomycini strain 615 against FLZ-resistant C. albicans clinical isolates in vitro.

Methods: S. monomycini strain 615 was cultured, and an aqueous crud extract containing its metabolites was prepared. The effects of extract were tested on five FLZ-resistant C. albicans isolates. Key pathogenic factors such as protease activity, biofilm formation, and gene expressions related to virulence (SAP1, SAP2, HWP1, and ERG11) and azole resistance (ERG11) were evaluated. Cytotoxicity of the extract (1.8-0.0008 µg/ml) was assessed on KYSE-30 esophageal epithelial cells using the MTT assay.

Results: Strain 615 showed strong antifungal activity with minimum inhibitory concentration (MIC) values of 0.0008-0.0035 µg/ml and minimum fungicidal concentration (MFC) values of 0.0017-0.0035 µg/ml after 48 hours. The extract significantly reduced ergosterol content by 31.81%, completely inhibited phospholipase and proteinase activities at 0.0035 µg/ml and suppressed biofilm formation at 0.0035-0.0140 µg/ml. Expression of all tested virulence genes decreased except for ERG11, indicating a possible mechanism to overcome azole resistance. The highest extract concentration caused 76.7% cytotoxicity in KYSE-30 cells after 72 hours.

Conclusion: S. monomycini strain 615 could serve as an alternative or adjunct therapy for FLZ-resistant oropharyngeal candidiasis in head and neck cancer patients, warranting further research to confirm safety and efficacy.
Keywords
Actinomycosis
Candida albicans
Drug resistance