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Abstract
ABSTRACT
Genomes of strains of the zoophilic dermatophyte Microsporum canis from invasive (disseminated and subcutaneous) and noninvasive (tinea capitis) infections were compared. Especially the disseminated strain showed significant syntenic rearrangements, including multiple translocations and inversions, and numerous SNPs and Indels in comparison to the noninvasive strain. In transcriptome analysis, both invasive strains were enriched for GO pathways related to components of the membrane, iron binding and heme binding, which possibly enables them to invade deeper into dermis and blood vessels. At 37 °C, invasive strains showed gene expression enriched for DNA replication, mismatch repair, N-glycan biosynthesis and ribosome biogenesis. The invasive strains were slightly less susceptible to multiple antifungal agents suggesting that acquired elevated drug resistance might be involved in the refractory disease courses. Patient with disseminated infection failed to respond to a combined antifungal treatment with itraconazole, terbinafine, fluconazole and posaconazole.
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1 Department of Dermatology and Venerology, Peking University First Hospital, Beijing, People’s Republic of China; Research Center for Medical Mycology, Peking University, Beijing, People’s Republic of China; National Clinical Research Center for Skin and Immune Diseases, Beijing, People’s Republic of China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, People’s Republic of China
2 Department of Dermatology and Venerology, Peking University First Hospital, Beijing, People’s Republic of China; Department of Dermatology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, People’s Republic of China
3 Department of Dermatology and Venerology, Peking University First Hospital, Beijing, People’s Republic of China; Department of Dermatology and Venerology, Beijing Jishuitan Hospital, Beijing, People’s Republic of China
4 Department of Dermatology and Venerology, Peking University First Hospital, Beijing, People’s Republic of China; Center of Expertise in Mycology of Radboud University Medical Center/Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
5 Department of Dermatology and Venerology, Peking University First Hospital, Beijing, People’s Republic of China; Research Center for Medical Mycology, Peking University, Beijing, People’s Republic of China; National Clinical Research Center for Skin and Immune Diseases, Beijing, People’s Republic of China; Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, People’s Republic of China; Center of Expertise in Mycology of Radboud University Medical Center/Canisius Wilhelmina Hospital, Nijmegen, The Netherlands