Decoding host cell interaction- and fluconazole-induced metabolic alterations and drug resistance in .

is an emerging drug-resistant pathogen associated with high mortality rates. This study aimed to explore the metabolic alterations and associated pathogenesis and drug resistance in fluconazole-treated -host cell interaction. Compared with controls, secreted metabolites from fluconazole-treated and fluconazole-treated -host cell co-culture demonstrated notable anti- activity. Fluconazole caused significant reductions in cell numbers and aggregated phenotype. Metabolites produced by with potential fungal colonization, invasion, and host immune evasion effects were identified. Metabolites known to enhance biofilm formation produced during -host cell interaction were inhibited by fluconazole. Fluconazole enhanced the production of metabolites with biofilm inhibition activity, including behenyl alcohol and decanoic acid. Metabolites with potential growth inhibition activity such as 2-palmitoyl glycerol, 1-tetradecanol, and 1-nonadecene were activated by fluconazole. Different patterns of proinflammatory cytokine expression presented due to fluconazole concentration and host cell type (fibroblasts versus macrophages). This highlights the immune response's complexity, emphasizing the necessity for additional research to comprehend cell-type-specific responses to antifungal therapies. Both host cell interaction and fluconazole treatment increased the expression of and genes, both associated with drug resistance. This study provides insights into pathogenesis in due to host cell interaction and fluconazole treatment. Understanding these interactions is crucial for enhancing fluconazole sensitivity and effectively combating .