Nonanal inhibits growth and virulence factors in Candida albicans

The recent surge in fungal infections, particularly caused by Candida albicans, is an important public health concern, especially among immunocompromised individuals. The current study aims to elucidate antifungal activity of nonanal against C. albicans (ATCC 90028) and clinical isolates. A range of quantitative methods was employed, including minimum inhibitory concentration (MIC) determination, cell cycle analysis, biofilm assays, microscopic observation of yeast to hyphal transitions, scanning electron microscopy of biofilms, and assessments of ergosterol inhibition and cell membrane damage. The results demonstrated that nonanal effectively inhibits the growth, morphogenesis, and biofilm formation at concentrations of 63 µg/ml, 125 µg/ml, and 16 µg/ml, respectively for C. albicans ATCC 90028, and at 125 µg/ml, 500 µg/ml, and 63 µg/ml, respectively for C1 and C2. Nonanal was able to induce cell cycle arrest and increase the reactive oxygen species (ROS) level in all strains of C. albicans. qRT-PCR analysis showed the downregulation of expression of key genes RAS1, BCY1, ECE1, CEK1, and HWP1 in ATCC 90028 and C1 isolte, while the negative regulator TUP1 was significantly upregulated ATCC 90028. Nonanal also affected the ergosterol synthesis and cell membrane in all the tested strains. Moreover, nonanal exhibited in vivo antifungal efficacy in silkworm animal model. These findings advance our understanding of nonanal as a novel potential antifungal agent, laying the groundwork for future antifungal strategies.