Antifungal susceptibility profiles and drug resistant mechanisms of clinical Lomentospora prolificans isolates.

We examined six different in vitro drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against L. prolificans We then annotated L. prolificans whole genome and located its Cyp51 and Fks1 genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in L. prolificans We found no amino acid changes in Cyp51 protein and no tandem repeats in 5' upstream region of the Cyp51 gene. However, we identified three intrinsic amino acid residues (G138S, M220I, T289A) in 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 of Fks1 hot spot regions and their contributions to echinocandin resistance needs future investigation. Overall, our findings support the notion that L. prolificans is intrinsically resistant to azoles and echinocandins. PMID: 32816726 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research