title: Pan-azole-resistant Candida tropicalis carrying homozygous erg11 mutations at position K143R: a new emerging superbug?
abstract: Candidaemia is a public health problem mainly in hospitalized individuals worldwide. In Brazil, Candida albicans is the most prevalent species that causes candidaemia, followed by Candida tropicalis and Candida parapsilosis . Few data on the abundance of antifungal resistance are available for Latin America.
  
  
  
  We analysed the frequency of azole and echinocandin resistance in Candida isolates ( n  =   75) collected between 2012 and 2014 at the University Hospital of Federal University of Juiz de Fora (Brazil). The primary targets erg11 (azoles) and fks1 (echinocandins) were sequenced and modelled at the protein level. Antifungal susceptibility testing was performed according to CLSI (M27-A3 and M27-S4) and according to EUCAST.
  
  
  
  The three most frequent species were C. albicans (38.0%), C. tropicalis (30.0%) and Candida glabrata (17.0%). Azole resistance was observed in 27.0% of all Candida isolates, while 20.0% of all isolates were echinocandin resistant. A novel mutation in erg11 at location K143R was found to be associated with phenotypically pan-azole-resistant C. tropicalis isolates. This mutation maps near the active binding site of erg11 and is likely to confer pan-azole resistance to C. tropicalis .
  
  
  
  A novel point mutation (K143R) located in the erg11 gene of C. tropicalis was found in pan-azole-resistant strains. According to our protein homology model, it is very likely that the mutation K143R causes pan-azole resistance in C. tropicalis . Moreover, an up-regulation of ABC transporters was observed, which can add up to a pan-azole-resistant phenotype.
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.|Laboratório de Química Biológica de Microorganismos, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariana I D S
authors.initials: MI
authors.lastname: Xisto
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Rita D F
authors.initials: RD
authors.lastname: Caramalho
authors.affiliation: Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Débora A S
authors.initials: DA
authors.lastname: Rocha
authors.affiliation: Laboratório de Bioquímica Microbiana, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferreira-Pereira
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Sartori
authors.affiliation: Laboratório de Química Biológica de Microorganismos, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Eliana
authors.initials: E
authors.lastname: Barreto-Bergter
authors.affiliation: Hospital Universitário, Universidade Federal de Juiz de Fora, Minas Gerais, Brazil.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Junqueira
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Lackner
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001938:Brazil; D041022:Candida tropicalis / Q000187:drug effects* / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology; D005964:Glucosyltransferases / Q000235:genetics; D006785:Hospitals, University; D006801:Humans; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D017354:Point Mutation; D017422:Sequence Analysis, DNA
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D003577:Cytochrome P-450 Enzyme System; D005964:Glucosyltransferases