Abstract:
Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25-72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin\'s promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections.
摘要:
侵袭性真菌(IF)疾病是全球主要的死亡原因,特别是在免疫受损的个体中。SARS-CoV-2大流行进一步加剧了这种情况,加剧共病IF感染,如鼻咽粘液菌病。在这里报道的工作中,它表明合子菌,真菌病的重要贡献者,对天然产物大蒜素敏感。证明了溶液中的大蒜素和大蒜素蒸气对Mucorales真菌的抑制作用。数学模型表明,大蒜素蒸气的功效与直接接触市售抗真菌剂两性霉素B(ampB)相当。此外,该研究揭示了大蒜素与非挥发性ampB之间的协同作用。评估了大蒜素溶液对人细胞系的毒性,发现与真菌孢子相比,细胞系中大蒜素的半数最大有效浓度(EC50)高25-72倍。真菌大蒜素的敏感性取决于孢子浓度,如跌落测试所示。这项研究显示了大蒜素的潜力,来自大蒜的含硫防御化合物,对抗合子菌真菌.这些发现强调了大蒜素在吸入鼻咽部感染中的应用前景,提出了一种新的治疗途径来对抗具有挑战性的真菌感染。