Therapeutic Intervention for Various Hospital Setting Strains of Biofilm Forming Candida auris with Multiple Drug Resistance Mutations Using Nanomaterial Ag-Silicalite-1 Zeolite

Abstract

Candida auris (C. auris), an emerging multidrug-resistant microorganism, with limited therapeutical options, is one of the leading causes of nosocomial infections. The current study includes 19 C. auris strains collected from King Fahd Hospital of the University and King Fahad Specialist Hospital in Dammam, identified by 18S rRNA gene and ITS region sequencing. Drug-resistance-associated mutations in ERG11, TAC1B and FUR1 genes were screened to gain 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 the ERG11 (F132Y and K143R) and TAC1B (H608Y, P611S and A640V) genes of C. auris strains, grouped into 3 clades. The prophylactic and therapeutic application of hydrothermally synthesized Ag-silicalite-1 (Si/Ag ratio 25) nanomaterial was tested against the 3 clades of clinical C. auris strains. 4wt%Ag/TiZSM-5 prepared using conventional impregnation technique was used for comparative study, and nano formulations were characterized using different techniques. The antibiofilm activity of nanomaterials was tested by cell kill assay, scanning electron microscopy (SEM) and light microscopy. Across all the clades of C. auris strains, 4 wt%Ag/TiZSM-5 and Ag-silicalite-1 demonstrated a significant (p = 1.1102 × 10−16) inhibitory effect on the biofilm’s survival rate: the lowest inhibition value was (10%) with Ag-silicalite-1 at 24 and 48 h incubation. A profound change in morphogenesis in addition to the reduction in the number of C.auris cells was shown by SEM and light microscopy. The presence of a high surface area and the uniform dispersion of nanosized Ag species displays enhanced anti-Candida activity, and therefore it has great potential against the emerging multidrug-resistant C. auris.

Zeolites as Ingredients of Medicinal Products

“…On this occasion, chabazite was synthesized in cotton fibres, thus creating a composite gauze that promoted clot formation in a short time without exothermic reaction. Recently, ZSM-5 and silicalite-1 zeolite were tested as against C. auris , a multidrug-resistant microorganism, and the results showed a considerable inhibitory effect [ 70 ].…”

Mining the nanotube-forming Bacillus amyloliquefaciens MR14M3 genome for determining anti-Candida auris and anti-Candida albicans potential by pathogenicity and comparative genomics analysis

“…By using the Kirby-Bauer disk diffusion method, bacterial potency against Candida albicans and Candida auris was determined. C. albicans strain CALB1 and C. auris CA1 were subjected to 18 S rRNA gene sequencing and ITS region sequencing to confirm the strains before use [8] , [36] . McFarland (0.5) standards of C. auris and C. albicans (0.8 × 10 6 to 1.2 × 10 6 cells/mL) were achieved for the Kirby-Bauer disk diffusion method.…”

“…Additionally, it is difficult to identify C. auris using standard microbiological methods [7] . Alternatives to traditional antifungal drugs that can inhibit the growth of C. auris have been proposed by drug repurposing approaches and nanomaterial-based studies, but promising drugs are still required for effective treatment [8] , [9] . The incidence and prevalence of C. auris have been increasing, especially in patients hospitalized for a long time and those who are immunocompromised [1] , [3] , [10] , [11] , [12] .…”

Comparative analysis of silver-nanoparticles and whey-encapsulated particles from olive leaf water extracts: Characteristics and biological activity

“…These green-synthesized NPs have shown promising applications in antibacterial [ 7 , 8 , 11 ] and anticancer therapies [ 12 – 14 ], highlighting their superiority over NPs produced by conventional methods. The Ag component of Ag-Silicalite-1 zeolite nanomaterial is an antimicrobial agent that can disrupt the cell membrane of Candida auris , leading to cell death and its broad-spectrum antimicrobial activity [ 15 ]. AgNPs have been shown to damage the ultrastructure of cancer cells [ 16 ] and cause the formation of reactive oxygen species (ROS), apoptosis [ 17 ], necrosis, and DNA damage [ 18 ].…”

“…They can also modulate various signaling pathways in the cell [ 19 ]. Thus, AgNPs offer a targeted approach that prevents undesirable side effects, has good pharmacokinetics and precise targeting, and reduces multidrug resistance [ 15 , 18 ].…”