Details

Autor(en) / Beteiligte

• Teixeira, Marcus M.
• Almeida-Paes, Rodrigo
• Bernardes-Engemann, Andréa R.
• Nicola, André M.
• de Macedo, Priscila M.
• Valle, Antonio Carlos F.
• Gutierrez-Galhardo, Maria Clara
• Freitas, Dayvison F.S.
• Barker, Bridget M.
• Matute, Daniel R.
• Stajich, Jason E.
• Zancopé-Oliveira, Rosely M.

Titel

Single nucleotide polymorphisms and chromosomal copy number variation may impact the Sporothrix brasiliensis antifungal susceptibility and sporotrichosis clinical outcomes

Ist Teil von

• Fungal genetics and biology, 2022-11, Vol.163, p.103743-103743, Article 103743

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• •Sporothrix brasiliensis isolates showed variable antifungal resistance phenotypes.•Infections caused by this species also present varied clinical manifestations.•Antifungal-resistant strains display significant copy number variation (CNVs).•CNVs affect genes involved in lipid and isoprenoid metabolism.•SNP‘s in the tac1 gene may also contribute to antifungal resistance. Feline-transmitted sporotrichosis has garnered attention due to the recent high incidence and the lack of efficient control in the epicenter of the epidemic, Rio de Janeiro, Brazil. Sporothrix brasiliensis is the major pathogen involved in feline-to-human sporotrichosis in Brazil and displays more virulent genotypes than the closely related species S. schenckii. Over the last two decades, several reports of antifungal-resistant strains have emerged. Sequencing and comparison analysis of the outbreak strains allowed us to observe that the azole non-wild-type S. brasiliensis strain CFP 1054 had significant chromosomal variations compared to wild-type strains. One of these variants includes a region of 231 Kb containing 75 duplicated genes, which were overrepresented for lipid and isoprenoid metabolism. We also identified an additional strain (CFP 1055) that was resistant to itraconazole and amphotericin B, which had a single nucleotide polymorphism in the tac1 gene. The patients infected with these two strains showed protracted clinical course and sequelae. Even though our sample size is modest, these results suggest the possibility of identifying specific point mutations and large chromosomal duplications potentially associated with antifungal resistance and clinical outcomes of sporotrichosis.