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JAC Advance Access published online on August 2, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl312
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received March 17, 2006
Revised July 6, 2006
Accepted July 7, 2006

Original article

Cationic lipids and surfactants as antifungal agents: mode of action

Débora B. Vieira 1 and Ana M. Carmona-Ribeiro 1 *

1 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, Avenida Lineu Prestes 748--Butantã, CEP 05513-970, São Paulo, Brazil

* To whom correspondence should be addressed.
Ana M. Carmona-Ribeiro, E-mail: mcribeir{at}iq.usp.br


  Abstract

Objectives: 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 (108 cfu/mL) yield limiting adsorption at 7.8 and 3.7 x 109 molecules per cell, respectively. Negatively charged C. albicans cells (106 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.

Keywords: Candida albicans; dioctadecyldimethylammonium bromide; hexadecyltrimethylammonium bromide; CTAB; adsorption; cell charge; lysis; antifungal activity.
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