The sensitivity of yeast and yeast-like cells to new lysosomotropic agents.
The lysosomotropic action of the compounds DM-11 and DMAL-12s against Saccharomyces cerevisiae, Schizosaccharomyces pombe and Candida albicans is species- and pH-dependent. At pH 6.0, DMAL-12s is less effective against S. cerevisiae and S. pombe but more effective against C. albicans than DM-11. At pH 8.0, DMAL-12s strongly inhibits the growth of S. cerevisiae but has only a marginal effect on the resistant C. albicans. S. pombe did not grow at pH 8.0. As shown by quinacrine accumulation, DM-11 causes a general intracellular acidification in all three species, while with DMAL-12s, the acidification is marginal. Morphological changes caused by DMAL-12s in S. cerevisiae affect the cell interior but not surface structures, while S. pombe cells exhibit a thickened and wrinkled cell wall, shrunken protoplast and "grainy" plasma membrane. A large number of blisters resembling lipid droplets were observed inside S. cerevisiae and S. pombe vacuoles. The high susceptibility of S. pombe cells to the action of DM-11 and DMAL-12s contrasts with the low sensitivity of S. pombe H+-ATPase to the agents. In our C. albicans isolate, DMAL 12s did not have an effect on cell morphology and appeared to be unable to penetrate the cells, especially at pH 8.0.
Krasowska
Anna
A
Institute of Genetics and Microbiology, Wrocław University, Przybyszewskiego 63-77, 51-148 Wrocław, Poland. aniak@microb.uni.wroc.pl
Chmielewska
Lucyna
L
Adamski
Ryszard
R
Luczyński
Jacek
J
Witek
Stanisław
S
Sigler
Karel
K
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D025141:Drug Resistance, Fungal; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008247:Lysosomes / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D015003:Yeasts / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000935:Antifungal Agents; C501402:undecyl 3-(dimethylamino)propionate; D015091:beta-Alanine; C085388:dodecyl 2-(N,N-dimethylamino)propionate; D006180:Proton-Translocating ATPases; D000409:Alanine