Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates.

is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the susceptibility of 8 drugs against 42 clinical isolates. All isolates showed high MICs to voriconazole (MIC>16 μg/ml), itraconazole (MIC>16 μg/ml), posaconazole (MIC>16 μg/ml), isavuconazole (MIC>16 μg/ml), amphotericin B (MIC>16 μg/ml), and terbinafine (MIC>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC>8 μg/ml), with the exception of miltefosine showing an MIC value of 4 μg/ml. We examined six different drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against We then annotated the whole genome and located its and genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in We found no amino acid changes in Cyp51 protein and no tandem repeats in the 5' upstream region of the gene. However, we identified three intrinsic amino acid residues (G138S, M220I, and T289A) in the Cyp51 protein that were linked to azole resistance. Likewise, two intrinsic amino acid residues (F639Y, W695F) that have reported to confer echinocandin resistance were found in Fks1 hot spot regions. In addition, three new amino acid alterations (D440A, S634R, and H1245R) were found outside Fks1 hot spot regions, and their contributions to echinocandin resistance need future investigation. Overall, our findings support the notion that is intrinsically resistant to azoles and echinocandins.