Mechanism of antifungal action of kanosamine.
The antibiotic kanosamine inhibited growth of Saccharomyces cerevisiae and a range of human pathogenic fungi, including Candida albicans. Kanosamine was transported into C. albicans cells by the glucose transport system and subsequently phosphorylated. The product of its intracellular metabolism, kanosamine-6-phosphate, was an inhibitor of the enzyme glucosamine-6-phosphate synthase. Inhibition was competitive in respect to one of the substrates, D-fructose-6-phosphate, with Ki = 5.9 mM, and was non-competitive in respect to the second substrate, L-glutamine. On the other hand, kanosamine-6-phosphate had no effect on the enzyme catalysing the next metabolic step, namely glucosamine-6-phosphate N-acetylase. The action of kanosamine on C. albicans cells resulted in profound morphological changes, inhibition of septum formation and cell agglutination. Experiments with S. cerevisiae mutants showed that the presence of the Cdr1p drug efflux pump did not affect the antifungal activity of kanosamine.
Janiak
A M
AM
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Milewski
S
S
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005944:Glucosamine / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors*; D010766:Phosphorylation
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; C014968:kanosamine; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D005944:Glucosamine