Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy.
Department of Biochemical Sciences, Laboratory Affiliated to Istituto Pasteur Italia Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy.
Int J Mol Sci. 2022 Jun 6;23(11):6345. doi: 10.3390/ijms23116345.
The increasing resistance to conventional antifungal drugs is a widespread concern, and a search for new compounds, active against different species of fungi, is demanded. Antimicrobial peptides (AMPs) hold promises in this context. Here we investigated the activity of the frog skin AMP Temporin G (TG) against a panel of fungal strains, by following the Clinical and Laboratory Standards Institute protocols. TG resulted to be active against (i) species and with MIC between 4 µM and 64 µM after 24 h of incubation; (ii) dermatophytes with MIC ranging from 4 to 32 µM, and (iii) strains with MIC of 128 µM. In addition, our tests revealed that TG reduced the metabolic activity of cells, with moderate membrane perturbation, as proven by XTT and Sytox Green assays, respectively. Furthermore, TG was found to be effective against some virulence factors; indeed, at 64 µM it was able to inhibit ~90% of yeast-mycelial switching, strongly prevented biofilm formation, and led to a 50% reduction of metabolic activity in mature biofilm cells, and ~30-35% eradication of mature biofilm biomass. Even though further studies are needed to deepen our knowledge of the mechanisms of TG antifungal activity, our results suggest this AMP as an attractive lead compound for treatment of fungal diseases.
抗药性的不断增加是一个普遍关注的问题,因此需要寻找新的化合物来对抗不同种类的真菌。抗菌肽 (AMPs) 在这方面具有很大的潜力。在此,我们根据临床和实验室标准协会的方案,研究了蛙皮抗菌肽 Temporin G (TG) 对一系列真菌菌株的活性。结果表明,TG 对以下真菌具有活性:(i) 属和 属,在孵育 24 小时后 MIC 值在 4 µM 到 64 µM 之间;(ii) 皮肤癣菌的 MIC 值在 4 到 32 µM 之间;(iii) 属的 MIC 值为 128 µM。此外,我们的测试还表明,TG 能够降低 细胞的代谢活性,中度破坏细胞膜,这一点通过 XTT 和 Sytox Green 测定分别得到证实。此外,TG 对一些真菌的毒力因子也有抑制作用;事实上,在 64 µM 时,它能够抑制约 90%的酵母-菌丝转换,强烈阻止生物膜的形成,并导致成熟生物膜细胞代谢活性降低 50%,成熟生物膜生物量减少约 30-35%。尽管需要进一步的研究来深入了解 TG 抗真菌活性的机制,但我们的结果表明,这种 AMP 是治疗真菌病的有吸引力的先导化合物。