title: Antifungal activity and mode of action of thymol and its synergism with nystatin against Candida species involved with infections in the oral cavity: an in vitro study.
abstract: BACKGROUND
  Limitations of antifungal agents used in the treatment of oral candidiasis, as the development of resistant strains, are known by the scientific community. In this context, the aim of this study was to evaluate the antifungal activity of thymol against Candida albicans, Candida tropicalis and Candida krusei strains and to determine its mode of action and synergistic effect when combined with the synthetic antifungal nystatin.
  
  
  METHODS
  The minimum inhibitory concentration (MIC) was determined using a microdilution technique, and the minimum fungicidal concentration (MFC) was determined via subculture sowing. The mode of action of thymol was established by verifying fungal growth in the presence of sorbitol or ergosterol. The fractional inhibitory concentration index (FIC) was determined using the checkerboard method.
  
  
  RESULTS
  Thymol presented an antifungal effect, with MICs of 39 μg/mL for C. albicans and C. krusei and 78 μg/mL for C. tropicalis. The results of the antifungal test remained unchanged in the presence of sorbitol; however, the MIC value of thymol against C. albicans increased eight times (from 39.0 to 312.5 μg/mL) in presence of exogenous ergosterol. The combination of thymol and nystatin reduced the MIC values of both products by 87.4%, generating an FIC index of 0.25.
  
  
  CONCLUSIONS
  Thymol was found to have a fungicidal effect on Candida species and a synergistic effect when combined with nystatin.
authors.affiliation: Postgraduate Program in Dentistry, School of Dentistry, Universidade Federal da Paraíba, Campus I, ZIP: 58.051-900, Joao Pessoa, Paraiba, Brazil. ricardodiasdecastro@yahoo.com.br.
authors.forename: Ricardo Dias
authors.initials: RD
authors.lastname: de Castro
authors.affiliation: School of Dentistry, Universidade Federal da Paraíba, ZIP: 58.051-900, Joao Pessoa, Paraiba, Brazil. triciamurielly@yahoo.com.br.
authors.forename: Trícia Murielly Pereira Andrade
authors.initials: TM
authors.lastname: de Souza
authors.affiliation: School of Dentistry, Universidade Federal da Paraíba, ZIP: 58.051-900, Joao Pessoa, Paraiba, Brazil. louisemdornelas@gmail.com.
authors.forename: Louise Morais Dornelas
authors.initials: LM
authors.lastname: Bezerra
authors.affiliation: Postgraduate Program in Dentistry, School of Dentistry, Universidade Federal da Paraíba, Campus I, ZIP: 58.051-900, Joao Pessoa, Paraiba, Brazil. gabriela_lacet@hotmail.com.
authors.forename: Gabriela Lacet Silva
authors.initials: GL
authors.lastname: Ferreira
authors.affiliation: Post-Graduate Program in Dentistry, State University of Paraiba, Campina Grande, Paraiba, Brazil. edjacosta@gmail.com.
authors.forename: Edja Maria Melo de Brito
authors.initials: EM
authors.lastname: Costa
authors.affiliation: Post-Graduate Program in Dentistry, State University of Paraiba, Campina Grande, Paraiba, Brazil. dralessandro@ibest.com.br.
authors.forename: Alessandro Leite
authors.initials: AL
authors.lastname: Cavalcanti
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000145:classification / Q000187:drug effects* / Q000254:growth & development; D002180:Candidiasis, Oral / Q000188:drug therapy / Q000382:microbiology*; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000382:microbiology; D009761:Nystatin / Q000494:pharmacology*; D013943:Thymol / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D009761:Nystatin; D013943:Thymol