Burmester Anke, Hipler Uta-Christina, Uhrlaß Silke, Nenoff Pietro, Singal Archana, Verma Shyam B, Elsner Peter, Wiegand Cornelia
Department of Dermatology, University Hospital Jena, Jena, Germany.
Laboratory of Medical Microbiology, Mölbis, Germany.
Mycoses. 2020 Nov;63(11):1175-1180. doi: 10.1111/myc.13150. Epub 2020 Sep 23.
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.
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.
Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay.
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.
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.
印度ITS基因型VIII须癣毛癣菌群体显示出大量不同的erg1（麦角固醇）突变体，这些突变体编码角鲨烯环氧酶，该酶催化麦角固醇生物合成的第一步。
阐明单erg1和双erg1须癣毛癣菌突变体中Ala448Thr位点的点突变的影响，因为这类突变体在印度真菌群体中大量存在。
使用基于微孔板激光比浊法（MLN）的生长试验分析在含氟康唑或特比萘芬的培养基中的生长情况。
Ala 448 Thr erg1单突变体对特比萘芬敏感，但约50%的分离株显示氟康唑耐药性增加，而95%的双突变体（Phe 397 Leu，Ala 448Thr）表现出对特比萘芬的联合耐药性及氟康唑耐药性增加。
新的印度须癣毛癣菌群体在erg1中显示出多个点突变。397位点的点突变先前已有描述，可导致对特比萘芬耐药。大部分双突变体对特比萘芬和氟康唑均耐药，表明两种突变组合具有选择性优势。
