Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; Interdepartmental Centre SITEIA.PARMA, University of Parma, Parma, Italy.
Int J Antimicrob Agents. 2018 Oct;52(4):500-505. doi: 10.1016/j.ijantimicag.2018.06.023. Epub 2018 Jul 7.
Candida albicans is a commensal yeast of the human body, able to form biofilms on solid surfaces such as implanted medical devices, and contributes to nosocomial infections. Biofilms have the capacity to resist higher levels of antifungals compared with planktonic cells, and can develop tolerance to commonly used treatments. The necessity to overcome acquired drug resistance and identify new active molecules with low toxicity is a significant problem. It has been reported that some antidepressants have antibacterial properties, but little is known regarding the effect of these drugs on fungi. This study demonstrated the capacity of three tricyclic antidepressants (doxepin, imipramine and nortriptyline) to inhibit the growth and biofilm formation of Candida spp. The antimicrobial potential of the drugs was assessed by studying gene expression, hyphae formation, biofilm growth and maturation. Their negative impact on the growth of C. albicans and other Candida spp. is shown in vitro and with the hepatic S9 system, which is preliminary to any in-vivo test. This study found that the antidepressants considered can inhibit not only hyphae and biofilm formation, but also kill cells in a mature biofilm. Moreover, cell lysis by nortriptyline was observed, along with its synergistic activity with amphotericin B. These findings suggest that tricyclic antidepressants, particularly nortriptyline, should be studied further in drug repositioning programmes to assess their antimycotic capacity in full.
白色念珠菌是人体共生的酵母，能够在植入的医疗设备等固体表面形成生物膜，并导致医院获得性感染。生物膜具有比浮游细胞更高水平的抗真菌能力，并且可以对常用治疗方法产生耐受性。克服获得性耐药性并识别具有低毒性的新活性分子是一个重大问题。据报道，一些抗抑郁药具有抗菌特性，但关于这些药物对真菌的影响知之甚少。本研究证明了三种三环类抗抑郁药（多虑平、丙咪嗪和去甲丙咪嗪）抑制念珠菌属生长和生物膜形成的能力。通过研究基因表达、菌丝形成、生物膜生长和成熟来评估药物的抗菌潜力。在体外和肝 S9 系统中研究了这些药物对 C. albicans 和其他念珠菌属生长的负面影响，这是任何体内试验的初步研究。本研究发现，所考虑的抗抑郁药不仅可以抑制菌丝和生物膜的形成，还可以杀死成熟生物膜中的细胞。此外，还观察到去甲丙咪嗪导致细胞裂解，并与两性霉素 B 具有协同活性。这些发现表明，三环类抗抑郁药，特别是去甲丙咪嗪，应在药物重新定位计划中进一步研究，以全面评估其抗真菌能力。
