Energy depletion protects Candida albicans against antimicrobial peptides by rigidifying its cell membrane.
Inhibitors of the energy metabolism, such as sodium azide and valinomycin, render yeast cells completely resistant against the killing action of a number of cationic antimicrobial peptides, including the salivary antimicrobial peptide Histatin 5. In this study the Histatin 5-mediated killing of the opportunistic yeast Candida albicans was used as a model system to comprehensively investigate the molecular basis underlying this phenomenon. Using confocal and electron microscopy it was demonstrated that the energy poison azide reversibly blocked the entry of Histatin 5 at the level of the yeast cell wall. Azide treatment hardly induced depolarization of the yeast cell membrane potential, excluding it as a cause of the lowered sensitivity. In contrast, the diminished sensitivity to Histatin 5 of energy-depleted C. albicans was restored by increasing the fluidity of the membrane using the membrane fluidizer benzyl alcohol. Furthermore, rigidification of the membrane by incubation at low temperature or in the presence of the membrane rigidifier Me(2)SO increased the resistance against Histatin 5, while not affecting the energy charge of the cell. In line, azide induced alterations in the physical state of the interior of the lipid bilayer. These data demonstrate that changes in the physical state of the membrane underlie the increased resistance to antimicrobial peptides.
Veerman
Enno C I
EC
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Vrije Universiteit and Universiteit van Amsterdam, 1081 BT Amsterdam, The Netherlands. eci.veerman@vumc.nl
Valentijn-Benz
Marianne
M
Nazmi
Kamran
K
Ruissen
Anita L A
AL
Walgreen-Weterings
Els
E
van Marle
Jan
J
Doust
Alexander B
AB
van't Hof
Wim
W
Bolscher
Jan G M
JG
Amerongen
Arie V Nieuw
AV
D000935:Antifungal Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001386:Azides / Q000494:pharmacology; D019905:Benzyl Alcohol / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003599:Cytoskeleton / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology; D025141:Drug Resistance, Fungal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D054808:Histatins; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D012471:Salivary Proteins and Peptides / Q000378:metabolism / Q000494:pharmacology
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D001386:Azides; D047630:Depsipeptides; C068075:HTN3 protein, human; D054808:Histatins; D012471:Salivary Proteins and Peptides; C057531:jasplakinolide; D019905:Benzyl Alcohol