Li Fang, Cheng Xi, Li Ling, Jiang Jinglu, Liu Yan, Mo Siyu, Jiang Wenxia, Liu Li, Baldi Salem, Long Nanbiao
Department of Medical Laboratory Diagnostics, School of Medical Technology, Shaoyang University, Shaoyang, China.
Front Microbiol. 2025 Aug 22;16:1613987. doi: 10.3389/fmicb.2025.1613987. eCollection 2025.
is an environmental opportunistic fungal pathogen, which can lead to invasive aspergillosis in immunocompromised individuals, and resistant to conventional antifungual agents has become a growing concern. This study investigated the antifungal activity and the molecular antifungal mechanisms of Cinnamaldehyde (CA) against , specifically its impact on metabolic pathways and protein metabolism. In susceptibility tests, CA was found to exhibit promising antifungal activity against in both solid and liquid culture (biomass) systems, with the minimum inhibitory concentration (MIC) determined as 40-80 μg/mL. Quantitative spore viability assays under elevated CA concentrations demonstrated that the antifungal efficacy of CA against is primarily attributable to its direct fungicidal mechanism. Interestingly, CA also showed equivalent antifungal activity against itraconazole- resistant strains R1 (ITZ, MIC 8 μg/mL) and R2 (ITZ, MIC 8 μg/mL), as it did against its parental strain Af293 (ITZ, MIC 1.5 μg/mL), suggesting its potential value to overcome resistance mechanisms associated with conventional antifungal therapies. Further proteomics and metabolomics analyses revealed that CA significantly affected the tricarboxylic acid (TCA) cycle and protein metabolism, with 167 differentially expressed proteins and 350 altered metabolites identified after 180 min of treatment (FC > 2 or <0.5, < 0.05, VIP > 1). Following treatment with CA, the protein expression of the putative translation initiation factor eIF4E3 (AFUB_051690), the putative leucyl-tRNA synthetase LeuRS (AFUB_093380), prolyl-tRNA synthetase ProRS (AFUB_010170) and the putative peptidyl-tRNA hydrolase Pth1 (AFUB_053480) exhibited a significant decrease. Moreover, deletion of resulted in a severe growth defect and hypersensitivity to CA, as evidenced by complete growth arrest at 30 and 45 μg/mL CA. Altogether, the results uncovered a novel antifungal mechanism of CA against and suggest that CA or its derivatives could be developed as effective antifungal drugs.
是一种环境机会性真菌病原体，可导致免疫功能低下个体发生侵袭性曲霉病，并且对传统抗真菌药物产生耐药性已成为一个日益受到关注的问题。本研究调查了肉桂醛（CA）对的抗真菌活性及其分子抗真菌机制，特别是其对代谢途径和蛋白质代谢的影响。在药敏试验中，发现CA在固体和液体培养（生物量）系统中均对表现出有前景的抗真菌活性，最小抑菌浓度（MIC）确定为40 - 80μg/mL。在升高的CA浓度下进行的定量孢子活力测定表明，CA对的抗真菌功效主要归因于其直接杀菌机制。有趣的是，CA对伊曲康唑耐药菌株R1（ITZ，MIC 8μg/mL）和R2（ITZ，MIC 8μg/mL）也显示出与对其亲本菌株Af293（ITZ，MIC 1.5μg/mL）同等的抗真菌活性，表明其在克服与传统抗真菌治疗相关的耐药机制方面的潜在价值。进一步的蛋白质组学和代谢组学分析表明，CA显著影响三羧酸（TCA）循环和蛋白质代谢，在处理180分钟后鉴定出167种差异表达蛋白和350种改变的代谢物（FC > 2或<0.5，<0.05，VIP > 1）。用CA处理后，推定的翻译起始因子eIF4E3（AFUB_051690）、推定的亮氨酰 - tRNA合成酶LeuRS（AFUB_093380）、脯氨酰 - tRNA合成酶ProRS（AFUB_010170）和推定的肽基 - tRNA水解酶Pth1（AFUB_053480）的蛋白表达显著下降。此外，的缺失导致严重的生长缺陷和对CA的超敏反应，在30和45μg/mL CA时完全生长停滞证明了这一点。总之，这些结果揭示了CA对的一种新的抗真菌机制，并表明CA或其衍生物可被开发为有效的抗真菌药物。
