Abstract
ABSTRACT Background The limited availability of antifungal drugs for candidiasis and the persistent problem of drug resistance, necessitates the urgent development of new antifungal drugs and alternative treatment options. Research design and methods This study examined the synergistic antifungal activity of the combination of eravacycline (ERV) and fluconazole (FLC) both in vitro by microdilution checkerboard assay and in vivo by Galleria mellonella model. The underlying synergistic mechanisms of this drug combination was investigated using RNA-sequencing and qPCR. Results ERV (2 μg/mL) + FLC (0.25–0.5 μg/mL) had strong synergistic antifungal activity against resistant Candida albicans (C. albicans) in vitro, as evidenced by a fractional inhibitory concentration index of 0.0044–0.0088. In vivo experiments in Galleria mellonella larvae infected with resistant C. albicans revealed that ERV (2 μg/larva) + FLC (1 μg/larva) improved survival rates and reduced fungal burden. The results of RNA-sequencing and qPCR showed that the mechanism of synergistic inhibition on resistant C. albicans was related to the inhibition of DNA replication and cell meiosis. Conclusions These results indicate that the combination of ERV and FLC effectively inhibits resistant C. albicans both in vitro and in vivo and lay the foundation for a potential novel treatment option for candidiasis.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
