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Biomedical subjects

Johanna Rhodes

Publications and source records attributed to Johanna Rhodes.

3 recordsLinked to original sources

First draft genome sequence of the emerging sexually transmitted dermatophyte Trichophyton mentagrophytes genotype VII.

Trichophyton mentagrophytes ITS-genotype VII (TMVII) is a globally emerging sexually transmitted dermatophyte causing severe skin infections characterised by painful, pustular lesions on the face, public area, genitalia, and trunk. To inform the prevention efforts, we present the first draft genomes of four TMVII isolates obtained from patients in the United Kingdom diagnosed between 2021 and 2025. We performed whole-genome sequencing and phylogenetic analysis based on single-nucleotide polymorphisms. We analysed the genetic relatedness of four TMVII isolates collected from UK patients, two had travel links to Spain and the Middle East. Two further isolates, including T. mentagrophytes ITS-genotype I/II obtained from a canine infection in the United Kingdom in 2025 and Trichophyton indotineae were sequenced for contextual analysis. We confirm that the TMVII strains studied here represent a highly clonal population, distinct from both zoophilic T. mentagrophytes genotype I/II and anthropophilic T. indotineae.

Humans

Emerging terbinafine-resistant Trichophyton indotineae between 2018 and 2023: a multinational genomic epidemiology study.

BACKGROUND: Trichophyton species cause the greatest burden of dermatophytosis worldwide, with the Trichophyton mentagrophytes species complex being particularly associated with the emergence of new aggressive infections. One emerging species, Trichophyton indotineae is notable for its clinical resistance to terbinafine antifungal treatment and rapid global spread. In this study we aim to characterise the epidemiology of this emerging pathogen using genomics. METHODS: In this retrospective genomic epidemiology study, to better understand the epidemiology of this disease, we sourced isolates collected from patients with severe cases of dermatophytosis (identified either by internal transcribed spacer sequencing or phenotypic characterisation) in the UK, Ireland, France, Canada, and India for the period 2014-23, including the T indotineae type strain from Japan. We used whole-genome sequencing to confirm 90 isolates were T indotineae, and antifungal susceptibility testing to assess susceptibility to terbinafine. FINDINGS: 103 cases of severe dermatophytosis caused by Trichophyton species collected between 2018 and 2023 in the UK, France, Canada, Ireland, and India were included in this study. Susceptibility testing indicated that 63 (70%) of 90 T indotineae isolates were resistant to terbinafine (minimum inhibitory concentration [MIC] ≥0·5 mg/L). Pairwise genetic distances showed very high identity with only 147 (range 1-414) single-nucleotide polymorphisms (SNPs) separating isolates that were nested within a monophyletic phylogeny, supporting a single evolutionary origin of T indotineae. Genome-wide analyses identified multiple non-synonymous SNPs in SQLE (ERG1), the squalene epoxidase target of terbinafine, that were associated with terbinafine in vitro resistance of 0·5 mg/L or higher. However, six isolates exhibited high MIC values without SQLE mutations, suggesting the presence of alternative resistance mechanisms. INTERPRETATION: That no clear geographical clustering of isolates was observed confirms the rapid transcontinental spread of T indotineae from its likely centre of diversity in Asia. Our findings highlight the importance of better genomic surveillance to understand and manage this severe and rapidly emerging terbinafine-resistant dermatophyte. FUNDING: None.

Terbinafine

Triazole-resistant Aspergillus fumigatus in the Netherlands between 1994 and 2022: a genomic and phenotypic study.

BACKGROUND: Aspergillus fumigatus is the main cause of invasive aspergillosis and triazole antifungals are the primary treatment option. The effectiveness of triazole therapy is hampered by the emergence of resistance, mainly caused by mutations in the cyp51A gene and a tandem repeat (TR) of 34 bases (TR34/Leu98His) and 46 bases (TR46/Tyr121Phe/Thr289Ala) in the promoter region, which correspond with signature triazole resistance phenotypes. We aimed to investigate the occurrence of triazole phenotype and genotype variation over a 29-year period in the Netherlands. METHODS: In this genomic and phenotypic study, we screened all clinical A fumigatus isolates from Dutch hospitals collected between Jan 6, 1994, and Dec 31, 2022, for resistance to triazole using agar-based methods, and characterised them by sequencing the cyp51A gene and in vitro susceptibility testing using the European Committee on Antimicrobial Susceptibility Testing reference method. Whole-genome sequencing was performed on selected isolates, including those harboring TR34 variants, high-frequency single-nucleotide polymorphisms, and wild-type strains. Clinical information such as age, underlying disease, diagnosis, therapy, and outcomes was collected for patients who had isolates cultured at the Radboud University Medical Centre, Nijmegen, Netherlands, between Jan 1, 2017, and Dec 31, 2022. FINDINGS: 1979 (15&#xb7;6%) of the screened 12&#x2009;679 A fumigatus isolates harboured cyp51A triazole resistance mutations, predominately TR34/Leu98His sensu stricto in 1338 (67&#xb7;6%) resistant isolates and TR46/Tyr121Phe/Thr289Ala sensu stricto in 332 (16&#xb7;8%) resistant isolates. Phenotype and genotype variations were observed in 325 (17&#xb7;2%) triazole resistant isolates harbouring a TR-resistance mechanism, including 12 cyp51A genotype variants. Whole-genome sequencing showed that isolates with combinations of TR34-based and TR46-based polymorphisms seemed to be derived from separate populations, but there was some overlap. 59 cases of proven or probable invasive aspergillosis were identified, including 13 triazole-resistant cases, of which three were caused by genotype variants. Mixed genotype infection was observed in 11 (84&#xb7;6%) of 13 triazole-resistant patients and the number of antifungal treatment switches was higher compared with triazole-susceptible disease (p<0&#xb7;0001). INTERPRETATION: Our study showed variation in triazole genotypes and phenotypes in clinical A fumigatus isolates with cyp51A-mediated resistance, some of which were cultured from triazole-resistant invasive aspergillosis cases. Triazole resistance variation and mixed A fumigatus genotypes represent a major challenge in clinical management of Aspergillus diseases because current molecular diagnostic tools will increasingly fail to predict the resistance phenotype, underscoring the need for improved detection methods. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and Wellcome Trust.

Aspergillus fumigatus