Clinical Isolate of a Multi-Antifungal-Resistant Trichophyton rubrum

doi:10.1128/aac.02393-21

. 2022 Apr 19;66(4):e0239321.

doi: 10.1128/aac.02393-21. Epub 2022 Mar 28.

Clinical Isolate of a Multi-Antifungal-Resistant Trichophyton rubrum

Rui Kano^{1

2}, Utako Kimura³, Hiromitsu Noguchi^{4

5}, Masataro Hiruma⁵

Affiliations

¹ Department of Veterinary Dermatology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa, Japan.
² Teikyo University Institute of Medical Mycology (TIMM), Hachioji, Tokyo, Japan.
³ Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan.
⁴ Ochanomizu Institute for Medical Mycology and Allergology, Toshima-ku, Tokyo, Japan.
⁵ Noguchi Dermatology Clinic, Kamimashiki-gun, Kumamoto, Japan.

PMID: 35341316
PMCID: PMC9017306
DOI: 10.1128/aac.02393-21

Clinical Isolate of a Multi-Antifungal-Resistant Trichophyton rubrum

Rui Kano et al. Antimicrob Agents Chemother. 2022.

. 2022 Apr 19;66(4):e0239321.

doi: 10.1128/aac.02393-21. Epub 2022 Mar 28.

Authors

Rui Kano^{1

2}, Utako Kimura³, Hiromitsu Noguchi^{4

5}, Masataro Hiruma⁵

Affiliations

¹ Department of Veterinary Dermatology, Nihon University College of Bioresource Sciences, Fujisawa, Kanagawa, Japan.
² Teikyo University Institute of Medical Mycology (TIMM), Hachioji, Tokyo, Japan.
³ Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan.
⁴ Ochanomizu Institute for Medical Mycology and Allergology, Toshima-ku, Tokyo, Japan.
⁵ Noguchi Dermatology Clinic, Kamimashiki-gun, Kumamoto, Japan.

PMID: 35341316
PMCID: PMC9017306
DOI: 10.1128/aac.02393-21

Abstract

The multi-antifungal drug-resistant strain (NUBS21012) of Trichophyton rubrum was isolated from a patient with recurrent tinea corporis. The resistant strain encoded Phe at codon 393 instead of Leu (L393F) in the squalene epoxidase (SQLE) gene. The expression of genes encoding ATP-binding cassette transporter proteins increased in the strain compared to that of other strains. This result provides evidence that ATP-binding cassette transporter proteins are closely associated with azole resistance.

Keywords: Trichophyton rubrum; azole; deletion mutation; dermatophytes; dermatophytoses; onychomycosis; squalene epoxidase; terbinafine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**FIG 1**
Transcript levels of the actin-encoding gene, *PDR1*, *MDR1*, *MDR2*, *MDR3*, and *MDR4* in TRF-resistant strains (NUBS21011 and NUBS21012) and TRF-susceptible strains (N45 and N46) of T. rubrum. All strains were cultured in SDB containing 0.05 μg/mL ITZ for 3 h at 28°C. Expression levels of all genes were normalized to that of the actin-encoding gene and are expressed as a relative quantity.

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References

1. Kwon-Chung KJ, Bennett EJ. 1992. Dermatophytoses, p 105–161. In Medical Mycology. Lea & Febiger, Philadelphia, PA.
1. Reiss E, Shadomy HJ, Lyon I. 2012. Dermatophytosis, p 527–566. In Fundamental medical mycology, Wiley-Blackwell, Hoboken, NJ.
1. Lipner SR, Scher RK. 2019. Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol 80:835–851. doi:10.1016/j.jaad.2018.03.062. - DOI - PubMed
1. Osborne CS, Leitner I, Favre B, Ryder NS. 2005. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemother 49:2840–2844. doi:10.1128/AAC.49.7.2840-2844.2005. - DOI - PMC - PubMed
1. Yamada T, Maeda M, Alshahni MM, Tanaka R, Yaguchi T, Bontems O, Salamin K, Fratti M, Monod M. 2017. Terbinafine resistance of Trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob Agents Chemother 61:e00115-17. doi:10.1128/AAC.00115-17. - DOI - PMC - PubMed

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[1] Kwon-Chung KJ, Bennett EJ. 1992. Dermatophytoses, p 105–161. In Medical Mycology. Lea & Febiger, Philadelphia, PA.

[2] Kwon-Chung KJ, Bennett EJ. 1992. Dermatophytoses, p 105–161. In Medical Mycology. Lea & Febiger, Philadelphia, PA.

[3] Reiss E, Shadomy HJ, Lyon I. 2012. Dermatophytosis, p 527–566. In Fundamental medical mycology, Wiley-Blackwell, Hoboken, NJ.

[4] Reiss E, Shadomy HJ, Lyon I. 2012. Dermatophytosis, p 527–566. In Fundamental medical mycology, Wiley-Blackwell, Hoboken, NJ.

[5] Lipner SR, Scher RK. 2019. Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol 80:835–851. doi:10.1016/j.jaad.2018.03.062. - DOI - PubMed

[6] Lipner SR, Scher RK. 2019. Onychomycosis: clinical overview and diagnosis. J Am Acad Dermatol 80:835–851. doi:10.1016/j.jaad.2018.03.062. - DOI - PubMed

[7] Osborne CS, Leitner I, Favre B, Ryder NS. 2005. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemother 49:2840–2844. doi:10.1128/AAC.49.7.2840-2844.2005. - DOI - PMC - PubMed

[8] Osborne CS, Leitner I, Favre B, Ryder NS. 2005. Amino acid substitution in Trichophyton rubrum squalene epoxidase associated with resistance to terbinafine. Antimicrob Agents Chemother 49:2840–2844. doi:10.1128/AAC.49.7.2840-2844.2005. - DOI - PMC - PubMed

[9] Yamada T, Maeda M, Alshahni MM, Tanaka R, Yaguchi T, Bontems O, Salamin K, Fratti M, Monod M. 2017. Terbinafine resistance of Trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob Agents Chemother 61:e00115-17. doi:10.1128/AAC.00115-17. - DOI - PMC - PubMed

[10] Yamada T, Maeda M, Alshahni MM, Tanaka R, Yaguchi T, Bontems O, Salamin K, Fratti M, Monod M. 2017. Terbinafine resistance of Trichophyton clinical isolates caused by specific point mutations in the squalene epoxidase gene. Antimicrob Agents Chemother 61:e00115-17. doi:10.1128/AAC.00115-17. - DOI - PMC - PubMed

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Clinical Isolate of a Multi-Antifungal-Resistant Trichophyton rubrum

Affiliations

Clinical Isolate of a Multi-Antifungal-Resistant Trichophyton rubrum

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Conflict of interest statement

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Abstract

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