Or the coding sequencemodifications (Table 1).Table 1. Minimal inhibitory concentrations (MICs), azole resistance mechanisms and TRESPERG typing assay of fifteen A. fumigatus strains. (AmB: amphotericin B; ITC: itraconazole; VCZ: voriconazole; POS: posaconazole; ISV: isavuconazole). Strains 1003 1003E 1003E2 1004 1004E 1004E2 1005.1 1005.2 1005.3 1005.4 TP1 TP2 TP3 TP4 TP5 CM2580 Source Patient Patient Patient Patient Patient Patient Patient Patient Patient Patient Bathroom Area Bathroom Space Space Manage Cyp51A Mutation TR34/L98H TR34/L98H TR34/L98H TR34/L98H TR34/L98H TR34/L98H TR34/L98H TR34/L98H TR34/L98H TR34/L98H G448S G448S TR34/L98H G448S WT WT MICs (mg/L) AmB 0.five 0.five 0.5 0.five 0.5 0.5 0.125 0.125 0.125 0.125 0.25 0.5 0.5 0.5 0.25.five 0.25 ITC 8 8 8 8 8 eight 8 eight eight 8 1 1 8 1 0.25 0.12 VCZ 4 four four four four four four 4 four 4 8 8 four eight 0.five 0.25 POS 0.five 0.5 0.5 0.5 0.5 0.five 0.five 0.5 0.five 0.five 0.5 0.25 0.5 0.25 0.06 0.03.25 ISV eight eight eight 8 eight 8 8 eight 8 eight four four 8 four 0.five 0.25 TRESPERG t10m1.Bcl-B Source 1g08Ae05 t10m1.1g08Ae05 t10m1.1g08Ae05 t10m1.1g08Ae05 t10m1.1g08Ae05 t10m1.1g08Ae05 t02m1.1g09e16 t02m1.1g09e16 t02m1.1g09e16 t02m1.1g09e16 t04Am1.3g05Ae07 t04Am1.3g05Ae07 t10m1.1g08Ae05 t04Am1.3g05Ae07 t04Am1.3g08Ae07 t01m5.5g03e11 Variety I I I I I I II II II II III III I III IV 3.2. Strains Genotyping Among all 15 A. fumigatus isolates incorporated in this study, four genotypes were identified based on the TRESPERG typing assay (Table 1). Clinical isolates (1003, 1003E, 1003E.two, 1004, 1004E, and 1004E.two) and also the environmental strain TP3 had the same genotype t10m1.1g08Ae05 named Kind I. The 4 remaining clinical strains (1005.1, 1005.two, 1005.3, and 1005.4) had the genotype t02m1.1g09e16corresponding to Form II. Among the other four environmental strains collected, 3 of them (TP1, TP2, and TP4) had been isogenic and characterized as Form III harboring the genotypet04Am1.3g05Ae07. Strain TP5 had a different genotype t04Am1.3g08Ae07 named Type IV. Strain CM2580 included as a wildtype susceptible strain had its own genotype diverse in the ones of your strains below study (Table 1). three.three. Antifungal Susceptibility Testing AFST to clinical azoles showed azole resistant MIC values in all strains tested except for the TP5 environmental strain which showed an azole-susceptible profile with ranges between 0.06 and 1 mg/L for all azoles tested. MIC values for amphotericin B wereJ. Fungi 2021, 7,5 ofconsidered susceptible for all fifteen isolates. Two different azole resistance profiles have been identified among all azole resistant isolates. All clinical strains along with the TP3 environmental isolate had precisely the same susceptibility profile consisting of8 mg/L to itraconazole, 4 mg/L to voriconazole, 0.five mg/L to posaconazole and 8 mg/L to isavuconazole. The other three environmental isolates (TP1, TP2, and TP4) had a MIC profile of 1 mg/L to itraconazole, eight mg/mL to voriconazole, 0.25.5 mg/L to posaconazole and 4 mg/L to isavuconazole (Table 1). 4. Discussion Azole-resistant A. fumigatus isolates from clinical and environmental origin are getting acknowledged worldwide [10,14]. Resistant strainsharbordifferent resistance mechanisms that confer particular susceptibility profiles to antifungal drugs applied inside the clinical setting and also within the atmosphere [16,43]. To date, the most prevalent azole resistance mechanism would be the TR34/L98H combination in Cyp51A, the S1PR4 Compound target for azole drugs, which has been mainly described from environmental isolates conferring multi-azole resistance [10]. In clinical samples the substi.