title: Changes in genotype and fluconazole susceptibility of isolates from patients with Candida glabrata in Tunisia.
abstract: Candida glabrata has emerged as an opportunistic pathogen of considerable importance in invasive and superficial infections.
  
  
  OBJECTIVE
  To analyze the development of fluconazole resistance in patients under treatment through epidemiological survey in our hospital.
  
  
  METHODS
  Twenty two patients (89 clinical strains) were collected. Molecular typing of isolates was performed by polymorphic markers. Analysis of gene expression was realized by reverse transcriptase-real time polymerase chain reactions (RT-qPCR).
  
  
  RESULTS
  Genetic analysis showed that 63% persists with apparently unchanged strains (n=14). Among them, four showed fluconazole resistance development. A strain replacement was observed in 6 patients and two patients selected more resistant isolates during the course of treatment. An analysis of Candida glabrata cerebellar degeneration-related protein 1 (CgCDR1), Candida glabrata cerebellar degeneration-related protein 2 (CgCDR2) and Candida glabrata sterol 14 alpha-demetylase Erg 11 (CgERG11) expression revealed an over-expression in 10 resistant isolates.
  
  
  CONCLUSIONS
  This study demonstrated that C. glabrata strain undergo frequent changes in vivo. The increase in CgCDR1 and CgCDR2 expression was the most mechanism associated with fluconazole resistance.
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Salma
authors.initials: S
authors.lastname: Abbes
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Imen
authors.initials: I
authors.lastname: Amouri
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Hayet
authors.initials: H
authors.lastname: Sellami
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Sourour
authors.initials: S
authors.lastname: Neji
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Houaida
authors.initials: H
authors.lastname: Trabelsi
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Fatma
authors.initials: F
authors.lastname: Cheikhrouhou
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Fattouma
authors.initials: F
authors.lastname: Makni
authors.affiliation: Laboratoire de parasitologie-mycologie, Aix-Marseille Université, AP-HM, CHU Timone, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Ranque
authors.affiliation: Laboratoire de biologie moléculaire, parasitaire et fongique, Faculté de médecine, Université de Sfax, Tunisie.
authors.forename: Ali
authors.initials: A
authors.lastname: Ayadi
mesh_terms: D041221:Candida glabrata / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D016533:Mycological Typing Techniques; D014416:Tunisia / Q000453:epidemiology
chemical_list: D015725:Fluconazole