Browsing by Author "Al-Dossary, Hanan Abdulrahman Nasser"

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Study of antibiotic resistance genes of Candida auris and nanoparticles as a potential therapeutic
(2022) Al-Dossary, Hanan Abdulrahman Nasser; بيرجيو، فرانسيس
In recent years, Candida auris (C. auris), a nosocomial infection, has emerged as a challenge, due to the limited therapeutic options and multidrug-resistance leading to a higher mortality rate. C. auris is reported to have developed resistance to various antifungal drugs such as fluconazole, amphotericin B, 5-fluorocytosine, caspofungin, etc., Hence, it becomes imperative to study and detect different resistant genes occurring among different strains isolated from the nosocomial infections. On the other hand, nanomaterials are known to have an exclusive characteristic in antimicrobial therapy through their controlled size and targeted drug delivery. Therefore, this study was conducted with the aim of identifying nineteen C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam then identified by 18S rRNA gene and ITS region sequencing technique and detecting the drug resistance-associated mutations in ERG11, TAC1B and FUR1 genes to get an insight into the pattern of drug resistance. Molecular identification was successfully achieved using 18S rRNA gene and ITS region and 5 drug resistance associated missense variants identified in ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains. Additionally, the current study offers the prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial against the nineteen clinical strains of C. auris, TiZSM-5, 4wt%Ag/TiZSM-5 were prepared using impregnation technique, Ag-silicalite-1 (25) and Ag-silicalite-1 (100) nanoformulations were characterized using different phases determination (XRD), surface area analysis (BET), diffuse reflectance UV-Visible spectroscopy (DRS-UV-Vis), thermogravimetric analysis and differential thermal analysis (TGA-DTA), morphological studies [(scanning electron microscopy/energy dispersive X-Rays spectroscopy (SEM/EDX) and transmission electron microscope (TEM)]. All the collected C. auris strains were subjected to antifungal efficacy by colony forming unit (CFU) technique and antibiofilm activity by employing cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the nineteen C. auris strains, 4wt% Ag/TiZSM-5 and Ag-silicalite-1 significantly inhibited the growth of the majority of C. auris strains and a significant inhibitory effect on biofilm’s survival rate, the lowest inhibition value was (10 %) with Ag-silicalite-1 at 24 and 48h incubation. A profound change in morphogenesis and in addition to the reduction in the number of C. auris cells was shown by SEM and light microscopy. The presence of high surface area and uniform dispersion of nanosized Ag species displays an enhanced anti-Candida activity and therefore it has a great potential against the emerging multidrug-resistant C. auris.
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