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Antimicrobial Agents and Chemotherapy, November 2008, p. 4081-4088, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01597-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Lactoferrin Induces Apoptosis-Like Cell Death in Candida albicans: Critical Role of K+-Channel-Mediated K+ Efflux{triangledown}

María T. Andrés,1 Monica Viejo-Díaz,1,2 and José F. Fierro1,2*

Laboratory of Oral Microbiology, School of Stomatology,1 Department of Functional Biology (Microbiology), Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain2

Received 11 December 2007/ Returned for modification 5 February 2008/ Accepted 10 August 2008

Human lactoferrin (hLf) induced an apoptosis-like phenotype in Candida albicans cells, which includes phosphatidylserine externalization, nuclear chromatin condensation, DNA degradation, and increased reactive oxygen species (ROS) production. Intracellular ROS accumulation was seen to correlate with candidacidal activity in hLf-treated cells. Mitochondrial activity was involved as indicated by mitochondrial depolarization and increased hLf resistance of cells preincubated with sordarin or erythromycin, the latter of which inhibits protein synthesis in mitoribosomes. Interestingly, Cl–- and K+-channel blockers prevented the hLf antimicrobial activity, but only when cells were pretreated with the blocking agent (tetraethylammonium) prior to the hLf-induced K+-release period. These results indicate for the first time that K+-channel-mediated K+ efflux is required for the progression of apoptosis-like process in yeast, suggesting that this essential apoptotic event of higher eukaryotes has been evolutionary conserved among species ranging from yeasts to humans.

* Corresponding author. Mailing address: Department of Functional Biology (Microbiology), Faculty of Medicine, University of Oviedo, C/Julián Clavería, 6, 33006 Oviedo, Spain. Phone: (34) 985 103643. Fax: (34) 985 103533. E-mail: jffierro{at}uniovi.es

{triangledown} Published ahead of print on 18 August 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 4081-4088, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.01597-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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