Read Aloud the Text Content

This audio was created by Woord's Text to Speech service by content creators from all around the world.

Text Content or SSML code:

Results: Firstly, I am going present us results in vitro. The graph represents the FIC index of different Candida auris strains. Red dashed line denotes the cut-off FIC index of 0.5 for synergistic interaction. As can be seen in the graph, no synergistic effect has been observed in any strain when combined F46 with FCZ. Drug interaction shows indifference in 75% of tested strains. While combinations of F46 with voriconazole or posaconazole showed similar activity, being mainly additive or synergistic. These combinations showed synergistic effects against 50% of strains tested and neither strain show antagonistic. It is remarkable effect of combination of F46 with posaconazole or voriconazole on Candida auris, which an emerging and multi-resistant strain. For biofilm disruption, four Candida auris strains were screened and our results didn’t show biofilm inhibitory activity of F46 at both 24 and 48 hours after treatment, although at high concentrations it seems to increase biofilm formation. Similar results were obtained in biofilm eradication. F46 showed no eradication effect on pre-formed C. auris biofilms compared to the control when the concentration of the compound or duration of treatment was increased. Except for strain FMR-17045, F46 tended to decrease the mass of biofilm formed, being significant only at a dose of 32 micrograms/ml. For the in vivo studies, it was decided to test the efficacy of the combination of flavone F46 with posaconazole, choosing two strains of C. auris for their different in vitro activities. Specifically, we chose strain JCM-15448 from an ear infection in Japan, considered the type strain, and strain FMR-17045 from an outbreak at La Fe Hospital in Valencia. In efficacy study, mice infected with the Japanese strain, all treatments, including the combination therapy, significantly prolonged survival in comparison to the control group, achieving 100% survival of the animals. The flavone F46 alone achieved 87% survival of animals at the end of experiment. With the Valencian strain, similar results in survival study were obtained, achieving 100% survival with all treatments, except for F46, which only achieved 75% survival. Regarding fungal load, it was reduced in the organs studied by all treatments, including combined therapy, after 8 and 23 days of infection with Japanese strain, except F42. However, a significant advantage of the combination over monotherapies was not observed in all organs. Even so the combination resulted in the greatest reduction of CFUs in mainly tissue, and in some cases, it even had the ability to clean or sterilize the tissue. Monotherapy with F46, with some exceptions like in lungs and liver, did not show efficacy in CFU reduction. Again, fungal burden of mice infected with Valencian strain showed similar results than observed in strain Japanese strain. In this case, the only notable difference is that after the treatment, on day 23, all treatments reduced the fungal burden in tissue after infection with strain FMR-17045, including flavone F42 in contrast to control group. The results of survival and fungal load, taken together, suggest that flavone probably acts on oxidative stress or on the inflammatory response, since at survival of the mice, flavone achieved similar results to AFG and PSC treatments, while in the fungal load, similar CFUs to the control group were obtained, indicating that flavone does not have a fungicidal effect, as it does not destroy the Candida in the organs. Conclusions In conclusion, our study demonstrates a potential antifungal activity of flavone in combination with PSC or VRC, showing mainly an additive or synergistic effect against Candida auris strains tested; nevertheless, the F46 alone does not show antibiofilm activity. And we corroborate in vivo studies that the combination of F46 with PSC shows better efficacy than other treatments, indicating a potential therapy of F46 in combination with PSC. However, it is necessary to optimize this combination to increase its effectiveness. ----- That is all, thank you for your attention/time and I will be delighted to answer any questions you might have.