Candida albicans strains deficient in CHS7, a key regulator of chitin synthase III, exhibit morphogenetic alterations and attenuated virulence.
Chitin is a structural polysaccharide present in most fungal cell walls, whose synthesis depends on a family of enzymic activities named chitin synthases (CSs). The specific role of each of them, as well as of their regulatory proteins, in cell morphogenesis and virulence is not well understood. Here, it is shown that most chitin synthesis in Candida albicans, one of the fungi most commonly isolated from opportunistic mycoses and infections, depends on CHS7. Thus, C. albicans chs7Delta null mutants showed reduced levels of chitin and CS activity, and were resistant to Calcofluor. Despite the sequence similarity and functional relationship with ScChs7p, CaChs7p was unable to restore CSIII activity in a Saccharomyces cerevisiae chs7Delta null mutant, because it was unable to direct ScChs3p export from the endoplasmic reticulum. C. albicans chs7Delta null mutants did not show any defect in growth rate, but yeast cells displayed minor morphogenetic defects affecting septum formation, and showed an increased tendency to form filaments. CaChs7p was not required for germ-tube emission, and null mutant strains underwent the dimorphic transition correctly. However, colony morphology appeared distinctively affected. chs7Delta hyphae were very curved and had irregular lateral walls, resulting in very compact colonies that seemed unable to spread out radially on the surface, unlike the wild-type. This growth pattern may be associated with the reduced virulence and high clearance rate observed when the chs7Delta strain was used in a murine model of infection. Therefore, CaChs7p is required for normal hyphal morphogenesis, suggesting that in C. albicans CSIII plays an important role in maintaining cell wall integrity, being essential when invading surrounding tissues.
Sanz
María
M
Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, R-219, Avda Campo Charro s/n, 37007 Salamanca, Spain.
Carrano
Lucia
L
Vicuron Pharmaceuticals, Gerenzano, Italy.
Jiménez
Cristina
C
Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, R-219, Avda Campo Charro s/n, 37007 Salamanca, Spain.
Candiani
Gianpaolo
G
Vicuron Pharmaceuticals, Gerenzano, Italy.
Trilla
José A
JA
Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, R-219, Avda Campo Charro s/n, 37007 Salamanca, Spain.
Durán
Angel
A
Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, R-219, Avda Campo Charro s/n, 37007 Salamanca, Spain.
Roncero
César
C
Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, R-219, Avda Campo Charro s/n, 37007 Salamanca, Spain.
D000818:Animals; D002176:Candida albicans / Q000166:cytology* / Q000235:genetics / Q000472:pathogenicity*; D002687:Chitin Synthase / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency* / Q000502:physiology; D009024:Morphogenesis; D009154:Mutation; D014774:Virulence
D008565:Membrane Proteins; D002687:Chitin Synthase