Mechanistic Investigations of a Novel Lactam Antifungal Agent Against Candida albicans

Candida albicans presents a major, yet underestimated challenge in clinical settings due to its increased resistance to treatment. This study intended to focus on the utility of a novel proprietary lactam molecule, a quorum sensing (QS) inhibitor, against C. albicans. We assessed isolate susceptibility to lactam treatment. In addition, RNA-Seq was used to assess lactam-induced transcriptional changes in phenotypically distinct C. albicans strains. The mechanistic basis of these transcriptional responses and a series of biochemical assays were performed using the reference strain SC5314. Our findings show that lactam influences multiple cellular processes, including cell wall integrity, efflux pump activity, oxidative stress responses and biofilm formation, with effects differing markedly between high and low biofilm formers. Vacuolation was observed with prolonged exposure to the lactam, and related genes in this process were identified and the phenotype confirmed. These results, supported by pathway analyses and mechanistic validation experiments, indicate that lactam's antifungal activity does not rely on a single mode of action. Rather, it appears to involve multiple mechanisms that vary across heterogeneous C. albicans isolates. These data indicate the potential therapeutic benefit of a novel fungicidal antifungal agent with broad-spectrum activity.