Identification of Promising Antifungal Drugs against Scedosporium and Lomentospora Species after Screening of Pathogen Box Library.
Rodrigo Rollin-PinheiroLuana Pereira Borba-SantosMariana Ingrid Dutra da Silva XistoYuri de Castro-AlmeidaVictor Pereira RochettiSonia RozentalEliana Barreto-BergterPublished in: Journal of fungi (Basel, Switzerland) (2021)
Fungal infections have been increasing during the last decades. Scedosporium and Lomentospora species are filamentous fungi most associated to those infections, especially in immunocompromised patients. Considering the limited options of treatment and the emergence of resistant isolates, an increasing concern motivates the development of new therapeutic alternatives. In this context, the present study screened the Pathogen Box library to identify compounds with antifungal activity against Scedosporium and Lomentospora. Using antifungal susceptibility tests, biofilm analysis, scanning electron microscopy (SEM), and synergism assay, auranofin and iodoquinol were found to present promising repurposing applications. Both compounds were active against different Scedosporium and Lomentospora, including planktonic cells and biofilm. SEM revealed morphological alterations and synergism analysis showed that both drugs present positive interactions with voriconazole, fluconazole, and caspofungin. These data suggest that auranofin and iodoquinol are promising compounds to be studied as repurposing approaches against scedosporiosis and lomentosporiosis.
Keyphrases
- candida albicans
- electron microscopy
- biofilm formation
- pseudomonas aeruginosa
- staphylococcus aureus
- end stage renal disease
- transcription factor
- ejection fraction
- induced apoptosis
- newly diagnosed
- chronic kidney disease
- prognostic factors
- cell death
- escherichia coli
- genetic diversity
- binding protein
- electronic health record
- intensive care unit
- cell cycle arrest
- cell proliferation
- drug induced
- endoplasmic reticulum stress
- smoking cessation
- patient reported
- bioinformatics analysis