Abstract
In this study, we induced terbinafine (TRF) resistance in a T. rubrum strain in vitro for 18 months then compared the genomes of the TRF-resistant (N42-3) and TRF-susceptible wild-type (N42WT) strains to identify mutations. In the SQLE gene, N42WT had no mutation while N42-3 had a F397L mutation. We sequenced approximately 22.53 Mb of the genomes of the N43WT and N42-3 strains. Other than the F397L mutation in SQLE, there were three other genetic mutations in three different genes that were found in N42-3, but not in N43WT; however, these three mutations were not detected in other TRF-resistant T. rubrum strains. From this genome sequencing analysis, the only variation that was confirmed to be associated with drug resistance in the genome of the TRF-resistant T. rubrum was a hotspot mutation in SQLE.
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References
Lipner SR, Scher RK. Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol. 2019;80:835–51. https://doi.org/10.1016/j.jaad.2018.03.062.
Monod M, Méhul B. Recent findings in onychomycosis and their application for appropriate treatment. J Fungi (Basel). 2019;5:20. https://doi.org/10.3390/jof5010020.
Sacheli R, Hayette MP. Antifungal resistance in dermatophytes: genetic considerations, clinical presentations and alternative therapies. J Fungi (Basel). 2021;7:983. https://doi.org/10.3390/jof7110983.
Hiruma J, Noguchi H, Hase M, Tokuhisa Y, Shimizu T, Ogawa T, Hiruma M, Harada K, Kano R. Epidemiological study of terbinafine-resistant dermatophytes isolated from Japanese patients. J Dermatol. 2021;48:564–7. https://doi.org/10.1111/1346-8138.15745.
Itoi S, Kano R, Hasegawa A, Kamata H. In vitro activities of antifungal agents against clinical isolates of dermatophytes from animals. J Vet Med Sci. 2012;74:1067–9. https://doi.org/10.1292/jvms.12-0057.
CLSI document M38–A2. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. 2nd ed. Philadelphia: Clinical Laboratory Standards Institute; 2008.
Lee H, Kim J, Lee J. Benchmarking datasets for assembly-based variant calling using high-fidelity long reads. BMC Genomics. 2023;2:148. https://doi.org/10.1186/s12864-023-09255-y.
Kano R, Noguchi H, Harada K, et al. Rapid molecular detection of terbinafine-resistant dermatophytes. Med Mycol J. 2021;62:41–4. https://doi.org/10.3314/mmj.21-00001.
Cornet L, D’hooge E, Magain N, Stubbe D, Packeu A, Baurain D, Becker P. The taxonomy of the Trichophyton rubrum complex: a phylogenomic approach. Microb Genom. 2021;7:000707. https://doi.org/10.1099/mgen.0.000707.
Acknowledgements
This work was supported by KAKENHI Grant Number 22K08442 from the Japan Society for the Promotion of Science (JSPS), and an Advanced Comprehensive Research Organization (ACRO) Incubation Grant (Grant No. In23-87) from Teikyo University.
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The research related to samples from humans has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors' institutional committee.
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Kano, R., Nojo, H. & Noguchi, H. Genomic Analysis of Antifungal Drug Resistance Induced in Trichophyton rubrum After Prolonged Culture with Terbinafine. Mycopathologia 188, 1079–1083 (2023). https://doi.org/10.1007/s11046-023-00795-1
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DOI: https://doi.org/10.1007/s11046-023-00795-1