Chitin biosynthesis in Candida albicans grown in vitro and in vivo and its inhibition by nikkomycin Z.
An N-acetyl-D-[14C]glucosamine radiolabel incorporation assay has been used to monitor chitin biosynthesis in whole cells of Candida albicans both in vitro and in vivo in two different mouse infection models, one using the peritoneal cavity as a chamber in which to add and retrieve cells and the other using infected kidneys. Specific labeling of chitin in alkali-insoluble material was confirmed by chitinase digestion, analysis of acid hydrolysates, and the use of nikkomycin Z as a probe. Nikkomycin Z was shown to strongly inhibit chitin biosynthesis in C. albicans grown in vitro and in vivo in both models. This demonstrates that nikkomycin Z-susceptible chitin synthase activity is present in C. albicans when the fungus is in its pathogenic state in vivo. The limited use of nikkomycin as a therapeutic agent is discussed.
Chapman
T
T
Division of Microbiology, Glaxo Group Research Ltd., Greenford, Middlesex, United Kingdom.
Kinsman
O
O
Houston
J
J
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D002686:Chitin / Q000096:biosynthesis*; D002688:Chitinases / Q000378:metabolism; D003864:Depression, Chemical; D051379:Mice
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002686:Chitin; C011952:nikkomycin; D002688:Chitinases