title: Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis.
abstract: BACKGROUND
  Sporotrichosis is a chronic subcutaneous mycosis of humans and animals, which is typically acquired by traumatic inoculation of plant material contaminated with Sporothrix propagules, or via animals, mainly felines. Sporothrix infections notably occur in outbreaks, with large epidemics currently taking place in southeastern Brazil and northeastern China. Pathogenic species include Sporothrix brasiliensis, Sporothrix schenckii s. str., Sporothrix globosa, and Sporothrix luriei, which exhibit differing geographical distribution, virulence, and resistance to antifungals. The phylogenetically remote species Sporothrix mexicana also shows a mild pathogenic potential.
  
  
  METHODS
  We assessed a genetically diverse panel of 68 strains. Susceptibility profiles of medically important Sporothrix species were evaluated by measuring the MICs and MFCs for amphotericin B (AMB), fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), posaconazole (PCZ), flucytosine (5FC), and caspofungin (CAS). Haplotype networks were constructed to reveal interspecific divergences within clinical Sporothrix species to evaluate genetically deviant isolates.
  
  
  RESULTS
  ITC and PCZ were moderately effective against S. brasiliensis (MIC90 = 2 and 2 μg/mL, respectively) and S. schenckii (MIC90 = 4 and 2 μg/mL, respectively). PCZ also showed low MICs against the rare species S. mexicana. 5FC, CAS, and FLC showed no antifungal activity against any Sporothrix species. The minimum fungicidal concentration ranged from 2 to >16 μg/mL for AMB against S. brasiliensis and S. schenckii, while the MFC90 was >16 μg/mL for ITC, VRC, and PCZ.
  
  
  CONCLUSIONS
  Sporothrix species in general showed high degrees of resistance against antifungals. Evaluating a genetically diverse panel of strains revealed evidence of multidrug resistant phenotypes, underlining the need for molecular identification of etiologic agents to predict therapeutic outcome.
authors.forename: Anderson Messias
authors.initials: AM
authors.lastname: Rodrigues
authors.forename: G Sybren
authors.initials: GS
authors.lastname: de Hoog
authors.forename: Débora
authors.initials: D
authors.lastname: de Cássia Pires
authors.forename: Raimunda Sâmia Nogueira
authors.initials: RS
authors.lastname: Brihante
authors.forename: José Júlio da Costa
authors.initials: JJ
authors.lastname: Sidrim
authors.forename: Marcos Fabio
authors.initials: MF
authors.lastname: Gadelha
authors.forename: Arnaldo Lopes
authors.initials: AL
authors.lastname: Colombo
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Cellular Biology Division, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. zpcamargo1@gmail.com.
authors.forename: Zoilo Pires
authors.initials: ZP
authors.lastname: de Camargo
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D014644:Genetic Variation; D006801:Humans; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D013175:Sporothrix / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D013174:Sporotrichosis / Q000382:microbiology*
chemical_list: D000935:Antifungal Agents
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