title: Effect of alkylphospholipids on Candida albicans biofilm formation and maturation.
abstract: OBJECTIVE
  The aim of this study was to evaluate miltefosine and four synthetic compounds (TCAN26, TC19, TC106 and TC117) for their in vitro inhibitory activity against Candida albicans planktonic and biofilm cells and investigate whether these compounds are able to inhibit the biofilm formation and to reduce the viability of mature C. albicans biofilm cells.
  
  
  METHODS
  The XTT reduction assay and transmission and scanning electron microscopy were employed to determine the inhibitory effects of the test compounds in comparison with amphotericin B and fluconazole against both planktonic cells and sessile cells in biofilms.
  
  
  RESULTS
  C. albicans planktonic cells were susceptible to miltefosine, TCAN26 and TC19, all alkylphospholipid compounds. Miltefosine and TCAN26 present a fungicidal activity with similar values of MIC and minimum fungicidal concentration (MFC), ranging from 2 to 8 mg/L. Cell treatment with sub-inhibitory concentrations of alkylphospholipids induced several ultrastructural alterations. In relation to biofilms, miltefosine reduced formation (38%-71%) and mature biofilms viability (32%-44%), at concentrations of 64 mg/L. TCAN26 also reduced biofilm formation (24%-30%) and mature biofilm viability (15%-20%), at concentrations of 64 mg/L. Although amphotericin B reduced biofilm formation similarly to miltefosine (51%-74%), its activity was lower on mature biofilms (24%-30%). Miltefosine antibiofilm activity was significantly higher than amphotericin B, on both formation and mature biofilms (P<0.05 and P<0.0001, respectively). Fluconazole was the least effective compound tested.
  
  
  CONCLUSIONS
  Promising antibiofilm activity was displayed by miltefosine and other alkylphosphocholine compounds, which could be considered a putative option for future treatment of candidaemia associated with biofilm formation, although further evaluation in in vivo systems is required.
authors.affiliation: Laboratório de Biologia Celular de Fungos, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Avenida Carlos Chagas Filho 373, Bloco C/sub-solo, Sala C0-026, Cidade Universitária, 21.941-902 Rio de Janeiro, Brazil.
authors.forename: Taissa V M
authors.initials: TV
authors.lastname: Vila
authors.forename: Kelly
authors.initials: K
authors.lastname: Ishida
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Prousis
authors.forename: Theodora
authors.initials: T
authors.lastname: Calogeropoulou
authors.forename: Sonia
authors.initials: S
authors.lastname: Rozental
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D010743:Phospholipids / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010933:Plankton / Q000187:drug effects / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D010743:Phospholipids; D010767:Phosphorylcholine; C039128:miltefosine