Abstract
BackgroundDermatomycoses are the most common fungal infections in the world affecting a significant part of the human and animal population. The majority of zoophilic infections in humans are caused by Trichophyton mentagrophytes. Currently, the first-line drug for both oral and topical therapy is terbinafine. However, an increasing number of cases that are difficult to be cured with this drug have been noted in Europe and Asia. Resistance to terbinafine and other allylamines is very rare and usually correlated with point mutations in the squalene epoxidase gene resulting in single amino acid substitutions in the enzyme, which is crucial in the ergosterol synthesis pathway.PurposeHere, we report terbinafine-resistant T. mentagrophytes isolates among which one was an etiological factor of tinea capitis in a man and three were obtained from asymptomatic foxes in Poland.MethodsWe used the CLSI protocol to determine antifungal susceptibility profiles of naftifine, amphotericin B, griseofulvin, ketoconazole, miconazole, itraconazole, voriconazole, and ciclopirox. Moreover, the squalene epoxidase gene of the terbinafine-resistant strains was sequenced and analysed.ResultsIn the genomes of all four resistant strains exhibiting elevated MICs to terbinafine (16 to 32 µg/ml), single-point mutations leading to Leu393Phe substitution in the squalene epoxidase enzyme were revealed. Among the other tested substances, a MIC50 value of 1 µg/ml was shown only for griseofulvin.ConclusionFinally, our study revealed that the terbinafine resistance phenomenon might not be acquired by exposure to the drug but can be intrinsic. This is evidenced by the description of the terbinafine-resistant strains isolated from the asymptomatic animals.
Highlights
Fungal infections of skin, hairs, and nails are the most prevalent mycoses worldwide with a high economic burden, as approximately $1.67 billion is spent on treatment each year [1,2,3]
Terbinafine exhibited the lowest M IC50 and M IC90 values in comparison with the other drugs, whereas four highly resistant isolates that were found resulted in the highest MICGM value of this substance for all isolates
The MIC50, MIC90, and Mode values of terbinafine, amphotericin, ketoconazole, miconazole, itraconazole, voriconazole, and ciclopirox against all T. mentagrophytes isolates were below 1 μg/ml, whereas those of griseofulvin and MIC90 of naftifine were above 1 μg/ml
Summary
Hairs, and nails are the most prevalent mycoses worldwide with a high economic burden, as approximately $1.67 billion is spent on treatment each year [1,2,3]. Most superficial infections caused by dermatophytes are successfully treated with terbinafine [1, 12] This antimycotic belongs to the allylamine group and is recommended as the first-line oral medication for the treatment of such infections [13,14,15]. Results In the genomes of all four resistant strains exhibiting elevated MICs to terbinafine (16 to 32 μg/ml), single-point mutations leading to Leu393Phe substitution in the squalene epoxidase enzyme were revealed. Conclusion our study revealed that the terbinafine resistance phenomenon might not be acquired by exposure to the drug but can be intrinsic. This is evidenced by the description of the terbinafine-resistant strains isolated from the asymptomatic animals
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