Candida albicans--do mycelia matter?
Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA-2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth.
Ryley
J F
JF
ICI Pharmaceuticals, Mereside, Macclesfield, UK.
Ryley
N G
NG
D000666:Amphotericin B / Q000627:therapeutic use; D000818:Animals; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D003470:Culture Media; D007672:Kidney Cortex / Q000382:microbiology; D007674:Kidney Diseases / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000382:microbiology; D051379:Mice; D014230:Triazoles / Q000627:therapeutic use
D003470:Culture Media; D014230:Triazoles; C058219:ICI 195739; D000666:Amphotericin B