Dosage-dependent roles of the Cwt1 transcription factor for cell wall architecture, morphogenesis, drug sensitivity and virulence in Candida albicans.
The Cwt1 transcription factor is involved in cell wall architecture of the human fungal pathogen Candida albicans. We demonstrate here that deficiency of Cwt1 leads to decreased beta1,6-glucan in the cell wall, while mannoproteins are increased in the cell wall of exponentially growing cells and are released into the medium of stationary phase cells. Hyphal morphogenesis of cwt1 mutants is reduced on the surfaces of some inducing media. Unexpectedly, the CWT1/cwt1 heterozygous strains shows some stronger in vitro phenotypes compared to the homozygous mutant. The heterozygous but not the homozygous strain is also strongly impaired for its virulence in a mouse model of systemic infection. We suggest that an intermediate dosage of Cwt1 affects phenotypes profoundly, while its complete absence may elicit compensatory responses of C. albicans.
Moreno
Inmaculada
I
GMCA Research Group, Departamento de Microbiología y Ecología, Facultad de Farmacia, Universidad de Valencia, Avenida Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Martinez-Esparza
María
M
Laforet
Leslie Carolina
LC
Sentandreu
Rafael
R
Ernst
Joachim F
JF
Valentin
Eulogio
E
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D002177:Candidiasis / Q000382:microbiology; D002473:Cell Wall / Q000378:metabolism / Q000648:ultrastructure; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D018628:Gene Dosage; D015966:Gene Expression Regulation, Fungal; D006720:Homozygote; D006801:Humans; D025301:Hyphae / Q000254:growth & development / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
D000935:Antifungal Agents; D004271:DNA, Fungal; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D014157:Transcription Factors; C025363:mannoproteins