Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l À1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the b-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR 34 /L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.

Background: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. Objective: Screening of environmental presence of azole-resistant A fumigatus in Iran.Methods: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar.Phenotypic MICs were obtained from selected, molecularly confirmed isolates.cyp51A gene sequencing and genotyping of azole-resistant isolates were done.Results: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR 46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype.Conclusion: This is the first report of A fumigatus with TR 46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region. K E Y W O R D SAspergillus fumigatus, azole resistance, compost, TR 34 /L98H, TR46/Y121F/T289A | 431 AHANGARKANI et Al.

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Background and Purpose:Microorganism-based synthesis of nanostructures has recently been noted as a green method for the sustainable development of nanotechnology. Nowadays, there have been numerous studies on the emerging resistant pathogenic bacteria and fungal isolates, the probable inability of bacteria and fungi to develop resistance against silver nanoparticles’ (SNPs) antibacterial, antifungal, antiviral and, particularly antibacterial activities. In this study, we aim to use the yeast Saccharomyces cerevisiae model for synthesis of SNPs and to investigate its antifungal activity against some isolates of Candida albicans.Materials and Methods:A standard strain of S. cerevisiae was grown in liquid medium containing mineral salt; then, it was exposed to 2 mM AgNO3. The reduction of Ag+ ions to metal nanoparticles was virtually investigated by tracing the color of the solution, which turned into reddish-brown after 72 hours. Further characterization of synthesized SNPs was performed afterwards. In addition, antifungal activity of synthesized SNPs was evaluated against fluconazole-susceptible and fluconazole-resistant isolates of Candida albicans. Results:The UV-vis spectra demonstrated a broad peak centering at 410 nm, which is associated with the particle sizes much less than 70 nm. The results of TEM demonstrated fairly uniform, spherical and small in size particles with almost 83.6% ranging between 5 and 20 nm. The zeta potential of SNPs was negative and equal to -25.0 (minus 25) mv suggesting that there was not much aggregation. Silver nanoparticles synthesized by S. cerevisiae, showed antifungal activity against fluconazole-susceptible and fluconazole-resistant Candida albicans isolates, and exhibited MIC90 values of 2 and 4 μg/ml, respectively.Conclusion:The yeast S. cerevisiae model demonstrated the potential for extracellular synthesis of fairly monodisperse silver nanoparticles.

Phylogenetic studies highlight Candida africana as an atypical variant within Candida albicans species complex which is dominantly recovered from vaginal specimens. This study aimed to characterize C. africana isolates from patients with vulvovaginal candidiasis (VVC) by molecular methods and in vitro susceptibilities. One hundred and fifty-six (48.44%) Candida strains were collected from 322 patients diagnosed with VVC. Of these, 114 (73.07%) were germ tube positive and presented green color on the chromogenic medium, thus classified as C. albicans species complex. One hundred and nine (95.61%) out of 114 isolates were identified as C. albicans, while five (4.38%) isolates were identical with C. africana based on hwp1 PCR. C. africana appeared to be highly susceptible to the tested antifungals. For all strains of C. africana, fluconazole MIC was 2-log2-dilution steps less active than amphotericin B, which in turn was 2-log2-dilution steps and 3-log2-dilution steps less active than other azoles and echinocandin agents, respectively. In conclusion, among the C. albicans species complex, C. albicans predominantly and C. africana rarely occur in vaginal mucosa. Due to limited information on molecular epidemiology of this novel yeast, more studies using molecular methods are needed to elucidate the inter- and intraspecific genomic variations of C. africana isolates.