Exploring the Antibiofilm Effect of Sertraline in Synergy with Cinnamomum verum Essential Oil to Counteract Candida Species

The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming ineffective against them. In recent decades, there has been a notable increase in systemic fungal infections, primarily caused by <i>Candida</i> species, which are progressively developing resistance to azoles. Moreover, <i>Candida</i> species biofilms are among the most common in clinical settings. In particular, they adhere to biomedical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. In recent years, many research programs have concentrated on the development of novel compounds with possible antimicrobial effects to address this issue, and new sources, such as plant-derived antimicrobial compounds, have been thoroughly investigated. Essential oils (EOs), among their numerous pharmacological properties, exhibit antifungal, antibacterial, and antiviral activities and have been examined at a global scale as the possible origin of novel antimicrobial compounds. A recent work carried out by our research group concerned the synergistic antibacterial activities of commercially available and chemically characterized <i>Cinnamomum verum</i> L. essential oil (<i>C. verum</i> EO) in association with sertraline, a selective serotonin reuptake inhibitor whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. The aim of this work was to explore the synergistic effects of <i>C. verum</i> EO with sertraline on both planktonic and sessile <i>Candida</i> species cells. Susceptibility testing and testing of the synergism of sertraline and <i>C. verum</i> EO against planktonic and sessile cells were performed using a broth microdilution assay and checkerboard methods. A synergistic effect was evident in both the planktonic cells and mature biofilms, with significant reductions in fungal viability. Indeed, the fractional inhibitory concentration index (FICI) was lower than 0.5 for all the associations, thus indicating significant synergism of the associations with the <i>Candida</i> strains examined. Moreover, the concentrations of sertraline able to inhibit Candida spp. strain growth and biofilm formation significantly decreased when it was used in combination with <i>C. verum</i> EO for all the strains considered, with a reduction percentage in the amount of each associated component ranging from 87.5% to 97%.