Cationic lipids and surfactants as antifungal agents: mode of action.
OBJECTIVE
To determine the mechanism of antimicrobial action for cationic lipid dioctadecyldimethylammonium bromide (DODAB) and hexadecyltrimethylammonium bromide (CTAB) against Candida albicans.


METHODS
Determination of DODAB or CTAB adsorption isotherms; cell viability; cell electrophoretic mobility (EM); and leakage of small phosphorylated compounds, proteins or DNA from fungus or haemoglobin from erythrocytes.


RESULTS
High affinity isotherms for CTAB and DODAB adsorption onto fungus cells (10(8) cfu/mL) yield limiting adsorption at 7.8 and 3.7 x 10(9) molecules per cell, respectively. Negatively charged C. albicans cells (10(6) cfu/mL) remain viable whereas positively charged ones die. At 0.3 mM CTAB or 0.01 mM DODAB, EM is zero and fungus viability is 50%. Cells start to die at submicellar CTAB concentrations and fungus lysis does not play a significant role in the mechanism of antifungal action. Over 0.1-10 mM CTAB or DODAB, there is no leakage of tested compounds from C. albicans cells despite the low cell viability. In contrast to the fungus, under isotonic conditions, cationic amphiphiles induce haemolysis over a range of low DODAB (>0.01 mM) and CTAB (>0.001 mM) concentrations.


CONCLUSIONS
The critical phenomenon determining antifungal effect of cationic surfactants and lipids is not cell lysis but rather the change of cell surface charge from negative to positive.
Vieira
Débora B
DB
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, Avenida Lineu Prestes 748-Butantã, CEP 05513-970 São Paulo, Brazil.
Carmona-Ribeiro
Ana M
AM
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002412:Cations / Q000494:pharmacology*; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000379:methods; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013499:Surface Properties; D013501:Surface-Active Agents / Q000494:pharmacology*
D000935:Antifungal Agents; D002412:Cations; D002593:Cetrimonium Compounds; D008055:Lipids; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C015831:dimethyldioctadecylammonium; D012967:Sodium Dodecyl Sulfate; D000077286:Cetrimonium