The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection.
Jesu Francis BorgioNoor Barak AlmandilPrathas SelvarajJ Sherlin JohnRahaf AlquwaieEman AlHasaniNorah F AlhurRazan AldahhanReem AlJindanDana AlmohazeySarah Ameen AlmoftyT Stalin DhasSayed AbdulazeezPublished in: Pharmaceutics (2024)
Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen Candida auris . In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti- C. auris activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase-dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti- auris activity in seven clinical C. auris isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by C. auris while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on C. auris , and significant ( p -value = 0.0057) shrinkage in the length of C. auris was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti- C . auris potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by C. auris and reduce the transmission of nosocomial infection.
Keyphrases
- candida albicans
- biofilm formation
- benign prostatic hyperplasia
- multidrug resistant
- pseudomonas aeruginosa
- lower urinary tract symptoms
- high throughput
- staphylococcus aureus
- escherichia coli
- end stage renal disease
- acinetobacter baumannii
- adverse drug
- drug resistant
- chronic kidney disease
- drug induced
- ejection fraction
- cystic fibrosis
- peritoneal dialysis
- prognostic factors
- gram negative
- cell proliferation
- climate change
- single cell
- cell death
- replacement therapy
- saudi arabia