Effect of Serotonin and Sertraline on Aspergillus

Background: By an accidential clinical observation we discovered that the psychopharmacon sertraline, a selective serotonin reuptake inhibitor (SSRI) has in vivo antifungal effects. Following studies showed sertraline to be able to kill Candida spp. and Aspergillus spp in vitro. Concentrations of sertraline in vitro necessary for fungicidal effects were relatively much higher compared to the serum levels which were achievable in vivo. Therefore, for in vivo outcome in our patients sertraline may have exerted its effect indirectly. In humans, SSRIs modify the concentration of 5 hydroxytryptamine (5 HT) since they act primarly at the 5 HT transporter protein. A block of the reuptake process of 5 HT leads to an increase of 5 HT. This fact led us to examine the direct influence of 5 HT on the viability of clinical isolates of Aspergillus spp. and Candida spp. We observed that 5 HT has in vitro antifungal activity. Aim: The data of antifungal activity of sertraline and 5 HT against Aspergillus spp. and Candida spp encourage us to study the mechanisms underlying these effects. We will investigate the following aspects: 1. Influence of sertraline and 5 HT on morphology of Aspergillus spp. 2. Influence of sertraline and 5 HT on physiology of Aspergillus spp. 3. Mechanism of fungicidal activities by sertraline and 5 HT: Induction of apoptosis or necrosis in Aspergillus spp. 4. Binding sites and accumulation of 5 HT inside or outside of Aspergillus spp. 5. Proteomic investigation: Identification of target-proteins in Aspergillus treated with 5 HT and sertraline Conclusion and future perspective: To examine the relationship between fungi and sertraline and 5 HT and to define the role of these substances in antifungal host defence could be of great help in identifying new antifungal targets and developing new antimycotics. After completing this study we will investigate the molecular mechanism by which 5 HT and sertraline act fungicidal.

By an accidential clinical observation we discovered that the psychopharmacon sertraline, a selective serotonin reuptake inhibitor (SSRI) has in vivo antifungal effects. Following studies showed sertraline to be able to kill Candida spp. and Aspergillus spp in vitro. Concentrations of sertraline in vitro necessary for fungicidal effects were relatively much higher compared to the serum levels which were achievable in vivo. Therefore, for in vivo outcome in our patients sertraline may have exerted its effect indirectly. In humans, SSRIs modify the concentration of 5 hydroxytryptamine (5 HT) since they act primarly at the 5 HT transporter protein. A block of the reuptake process of 5 HT leads to an increase of 5 HT. This fact led us to examine the direct influence of 5 HT on the viability of clinical isolates of Aspergillus spp. and Candida spp. We observed that 5 HT has in vitro antifungal activity. Aim: The data of antifungal activity of sertraline and 5 HT against Aspergillus spp. and Candida spp encourage us to study the mechanisms underlying these effects. We will investigate the following aspects: 1. Influence of sertraline and 5 HT on morphology of Aspergillus spp. 2. Influence of sertraline and 5 HT on physiology of Aspergillus spp. 3. Mechanism of fungicidal activities by sertraline and 5 HT: Induction of apoptosis or necrosis in Aspergillus spp. 4. Binding sites and accumulation of 5 HT inside or outside of Aspergillus spp. 5. Proteomic investigation: Identification of target-proteins in Aspergillus treated with 5 HT and sertraline Conclusion and future perspective: To examine the relationship between fungi and sertraline and 5 HT and to define the role of these substances in antifungal host defence could be of great help in identifying new antifungal targets and developing new antimycotics. After completing this study we will investigate the molecular mechanism by which 5 HT and sertraline act fungicidal.