CYP51 Mutations in the Fusarium solani Species Complex: First Clue to Understand the Low Susceptibility to Azoles of the Genus Fusarium

Members of species complex (FSSC) are cosmopolitan filamentous fungi responsible for invasive fungal infections in immunocompromised patients. Despite the treatment recommendations, many strains show reduced sensitivity to voriconazole. The objective of this work was to investigate the potential rel...

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Bibliographic Details
Published in:Journal of fungi (Basel) 2022-05, Vol.8 (5), p.533
Main Authors: Vermeulen, Pierre, Gruez, Arnaud, Babin, Anne-Lyse, Frippiat, Jean-Pol, Machouart, Marie, Debourgogne, Anne
Format: Article
Language:English
Subjects:
Amino acid sequence
antifungal susceptibility
azole
Azoles
Binding sites
CYP51
CYP51 protein
Enzymes
Fungi
Fusarium
Fusarium solani
Genes
Immunocompromised hosts
Life Sciences
Microbiology and Parasitology
Mutation
Pathogens
Proteins
Voriconazole
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Summary:Members of species complex (FSSC) are cosmopolitan filamentous fungi responsible for invasive fungal infections in immunocompromised patients. Despite the treatment recommendations, many strains show reduced sensitivity to voriconazole. The objective of this work was to investigate the potential relationship between azole susceptibility and mutations in CYP51 protein sequences. Minimal inhibitory concentrations (MICs) for azole antifungals have been determined using the CLSI (Clinical and Laboratory Standards Institute) microdilution method on a panel of clinical and environmental strains. , and genes for each strain have been sequenced using the Sanger method. Amino acid substitutions described in multiple azole-resistant (mtrAf) strains have been sought and compared with other complexes' strains. Our results show that FSSC exhibit point mutations similar to those described in mtrAf. Protein sequence alignments of CYP51A, CYP51B and CYP51C have highlighted different profiles based on sequence similarity. A link between voriconazole MICs and protein sequences was observed, suggesting that these mutations could be an explanation for the intrinsic azole resistance in the genus . Thus, this innovative approach provided clues to understand low azole susceptibility in FSSC and may contribute to improving the treatment of FSSC infection.
ISSN:2309-608X
2309-608X
DOI:10.3390/jof8050533