The Potential of Dutasteride for Treating Multidrug-Resistant <i>Candida auris</i> Infection
J. Francis Borgio,
Noor B. Almandil,
Prathas Selvaraj,
J. Sherlin John,
Rahaf Alquwaie,
Eman AlHasani,
Norah F. Alhur,
Razan Aldahhan,
Reem AlJindan,
Dana Almohazey,
Sarah Almofty,
T. Stalin Dhas,
Sayed AbdulAzeez
Affiliations
J. Francis Borgio
Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Noor B. Almandil
Department of Clinical Pharmacy Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Prathas Selvaraj
Entomology Research Unit (ERU), Department of Zoology, St. Xavier’s College (Autonomous), Palayamkottai, Affiliated to Manonmaniam Sundaranar University, Tirunelveli 627002, Tamil Nadu, India
J. Sherlin John
Entomology Research Unit (ERU), Department of Zoology, St. Xavier’s College (Autonomous), Palayamkottai, Affiliated to Manonmaniam Sundaranar University, Tirunelveli 627002, Tamil Nadu, India
Rahaf Alquwaie
Master Program of Biotechnology, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Eman AlHasani
Master Program of Biotechnology, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Norah F. Alhur
Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Razan Aldahhan
Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Reem AlJindan
Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 40017, Saudi Arabia
Dana Almohazey
Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Sarah Almofty
Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
T. Stalin Dhas
Centre for Ocean Research (DST—FIST Sponsored Centre), MoES-Earth Science & Technology Cell, Sathyabama Institute of Science and Technology, Chennai 600119, India
Sayed AbdulAzeez
Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
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.
