| Autor: |
Borgio JF; Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Almandil NB; Department of Clinical Pharmacy Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Selvaraj P; Entomology Research Unit (ERU), Department of Zoology, St. Xavier's College (Autonomous), Palayamkottai, Affiliated to Manonmaniam Sundaranar University, Tirunelveli 627002, Tamil Nadu, India., John JS; Entomology Research Unit (ERU), Department of Zoology, St. Xavier's College (Autonomous), Palayamkottai, Affiliated to Manonmaniam Sundaranar University, Tirunelveli 627002, Tamil Nadu, India., Alquwaie R; Master Program of Biotechnology, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., AlHasani E; Master Program of Biotechnology, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Alhur NF; Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Aldahhan R; Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., AlJindan R; Department of Microbiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 40017, Saudi Arabia., Almohazey D; Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Almofty S; Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Dhas TS; Centre for Ocean Research (DST-FIST Sponsored Centre), MoES-Earth Science & Technology Cell, Sathyabama Institute of Science and Technology, Chennai 600119, India., AbdulAzeez S; Department of Genetic Research, Institute for Research and Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia. |
| Abstrakt: |
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. |
