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. 2021 Aug;64(8):936-946.
doi: 10.1111/myc.13286. Epub 2021 Apr 25.

Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2

Tsuyoshi Yamada  1   2 , Takashi Yaguchi  3 , Takashi Tamura  4 , Christine Pich  5 , Karine Salamin  5 , Marc Feuermann  6 , Michel Monod  5
Affiliations

Itraconazole resistance of Trichophyton rubrum mediated by the ABC transporter TruMDR2

Tsuyoshi Yamada et al. Mycoses. 2021 Aug.

Abstract

Background: Dermatophytes showing reduced sensitivity to antifungal agents have emerged in several countries. One terbinafine resistant strain of Trichophyton rubrum, TIMM20092, also showed reduced sensitivity to itraconazole (ITC) and voriconazole (VRC). The expression of two genes (TruMDR2 and TruMDR3) encoding multidrug transporters of the ABC family was found to be highly up-regulated in this strain. Deletion of TruMDR3 in TIMM20092 abolished its resistance to VRC but only slightly reduced its resistance to ITC.

Objectives: We examined the potential of T rubrum to develop resistance to ITC by analysing the mechanism of ITC resistance in TIMM20092.

Methods: The deletion of TruMDR2 by gene replacement was performed in TIMM20092 and one TruMDR3-lacking mutant (∆TruMDR3) previously generated from TIMM20092. TruMDR2 single and TruMDR2/TruMDR3 double mutants (∆TruMDR2 and ∆TruMDR2/3) were successfully obtained, respectively.

Results: The suppression of TruMDR2 was shown to abolish resistance to ITC in TIMM20092 and the TruMDR3-lacking mutant, strongly suggesting that TruMDR2 is a major contributor to ITC resistance in TIMM20092.

Conclusions: Our study highlights the possible role of the ABC transporter TruMDR2 in ITC resistance of T. rubrum.

Keywords: Trichophyton rubrum; ABC transporters; TruMDR2; dermatophytes; itraconazole resistance.

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References

REFERENCES

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