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. 2020 Nov;63(11):1175-1180.
doi: 10.1111/myc.13150. Epub 2020 Sep 23.

Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance

Anke Burmester  1 , Uta-Christina Hipler  1 , Silke Uhrlaß  2 , Pietro Nenoff  2 , Archana Singal  3 , Shyam B Verma  4 , Peter Elsner  1 , Cornelia Wiegand  1
Affiliations

Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance

Anke Burmester et al. Mycoses. 2020 Nov.

Abstract

Background: The Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis.

Objectives: Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population.

Methods: Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay.

Results: Ala 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance.

Conclusion: The new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.

Keywords: Trichophyton mentagrophytes; ergosterol biosynthesis; squalene epoxidase; terbinafine resistance.

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References

REFERENCES

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