Global Emergence of Antifungal-Resistant Dermatophytosis Caused by Trichophyton indotineae (Formerly T. mentagrophytes ITS Genotype VIII): A Genomic Investigation Involving 14 Countries.
Amanda Ribeiro Dos Santos, Silke Uhrlaß, Pietro Nenoff, Jeremy A W Gold, Mohammed Saiful Islam Bhuiyan, Srikumar Goturu, Lalitha Gade, Ujwal R Bagal, Joyce G Peterson, Nathan P Wiederhold, Shawn R Lockhart, Helle Järv, Ammar F Hameed, Jacek Szepietowski, Resham Vasani, Archana Singal, Lindsay Parnell, Brian Schwem, Tom Chiller, Anastasia P Litvintseva, Nancy A Chow, Shyam B Verma
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引用次数: 0
Abstract
Background and objective: Trichophyton indotineae is a globally emerging, frequently antifungal-resistant fungus causing severe dermatophytosis. To inform prevention efforts, we analysed the genomic epidemiology and resistance to terbinafine (first-line oral antifungal) from a collection of multinational T. indotineae isolates collected from patients with clinically suspected dermatophytosis during 2016-2023.
Methods: We performed whole genome sequencing and phylogenetic tree analysis based on single-nucleotide polymorphisms (SNPs). T. indotineae phylogenetic results were correlated with patient demographic characteristics and isolate terbinafine susceptibility profiles that were determined by antifungal susceptibility testing and squalene epoxidase gene sequencing. Trichophyton mentagrophytes and Trichophyton interdigitale isolates from the USA, and Trichophyton rubrum isolates from three countries were added for contextual analysis.
Results: Among 347 T. indotineae isolates, 227 (65%) were in vitro resistant to terbinafine. Countries represented were India (43%); Germany (21%); Bangladesh (8%); United States (8%); United Arab Emirates (7%); Iraq (5%); Finland (3%); Poland (2%); Austria, Canada, Cambodia, Estonia, Singapore, and Switzerland (each < 1%). Median SNP difference between isolates was 106 SNPs (range: 0-392). Clustering by age, sex, or country was not observed. One subcluster was composed of terbinafine-resistant isolates with a specific squalene epoxidase gene mutation (F397L) and was widely dispersed among 10 countries. Intra-species genomic diversity was greater among 19 T. rubrum isolates (260 SNPs [range: 73-1038]), or among 10 T. mentagrophytes/T. interdigitale isolates from the USA compared with the intra-species diversity of the T. indotineae isolates.
Conclusions: Our findings corroborate T. indotineae's recent emergence and ongoing international transmission and suggest the rapid spread of a subset of terbinafine-resistant isolates. Continued efforts are necessary to mitigate this pathogen's spread.
期刊介绍：
The journal Mycoses provides an international forum for original papers in English on the pathogenesis, diagnosis, therapy, prophylaxis, and epidemiology of fungal infectious diseases in humans as well as on the biology of pathogenic fungi.
Medical mycology as part of medical microbiology is advancing rapidly. Effective therapeutic strategies are already available in chemotherapy and are being further developed. Their application requires reliable laboratory diagnostic techniques, which, in turn, result from mycological basic research. Opportunistic mycoses vary greatly in their clinical and pathological symptoms, because the underlying disease of a patient at risk decisively determines their symptomatology and progress. The journal Mycoses is therefore of interest to scientists in fundamental mycological research, mycological laboratory diagnosticians and clinicians interested in fungal infections.
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