Abstract
Candida albicans, normally a human commensal, can cause fatal systemic infections under certain circumstances. Its unique ability to switch from yeast to hyphal growth in response to various environmental signals is inherent to its pathogenicity. Filamentation is regulated by multiple pathways including a Cph1-mediated mitogen-activated protein kinase pathway, an Efg1-mediated cAMP/PKA pathway, and a Cph2 pathway. To gain a general picture of how these various signaling pathways regulate differential gene expression during filamentation, we have constructed a partial C. albicans DNA array of 7,000 genes and used it to study the gene expression profiles using various mutants and growth conditions. By combining this novel technology with a new liquid medium in which cph1/cph1 is defective in filamentation, previously identified differentially expressed genes (ECE1, HWP1, HYR1, RBT1, SAPs5-6, and RBT4) are found to be regulated by all three pathways. In addition, two novel genes, DDR48 and YPL184, have been found to be differentially regulated during hyphal development and by all three pathways. This suggests that distinct filamentation signaling pathways converge to regulate a common set of differentially expressed genes. As one of the mechanisms for the observed convergence, we find that the transcription of a key regulator, TEC1, is regulated by Efg1 and Cph2. Importantly, most of the genes regulated by multiple filamentation pathways encode known virulence factors. Perhaps, C. albicans utilizes converging pathways to regulate its vital virulence factors to ensure its survival and pathogenicity in various host environments.
Highlights
Candida albicans is a common human commensal often associated with superficial colonization of the mucous epithelium
The Efg1mediated cAMP pathway is thought to be distinct from the Cph1-mediated mitogen-activated protein (MAP) kinase pathway, because the cph1/cph1 efg1/efg1 double mutant has a greater defect in hyphal development and virulence than either single mutant [3]
If we extend the scale of the DNA array to include all C. albicans open reading frames (ORFs), or if we include genes with less dramatic changes in gene expression from our partial array, we may identify genes regulated by Cph1 or Cph2
Summary
Candida albicans is a common human commensal often associated with superficial colonization of the mucous epithelium. A transcription factor homologous to Saccharomyces cerevisiae, Ste, plays a role in hyphal development on certain solid media in C. albicans [6]. As in S. cerevisiae, Cph in C. albicans is regulated by a mitogen-activated protein (MAP) kinase cascade that includes Cst, Hst, and Cek1 [7,8,9]. A basic helixloop-helix protein similar to Phd of S. cerevisiae and StuA of Aspergillus nidulans, plays a major role in regulating hyphal development in C. albicans [3, 10]. A new member of the TEA/ATTS family of transcription factors, Tec, has been shown to regulate hyphal development and virulence in C. albicans [13]. A potential transcription factor with a zinc finger motif, regulates filamentous growth in response to embedded conditions. Wild type ura3ϻ1 imm434/ura3ϻ1 imm434 his1ϻhisG/his1ϻhisG arg4ϻhisG/arg4ϻhisG cph2ϻARG4/cph2ϻURA3 ura3ϻ1 imm434/ura3ϻ1 imm434 his1ϻhisG/his1ϻhisG arg4ϻhisG/arg4ϻhisG cph1ϻhisG/cph1ϻhisG-URA3-hisG ura3ϻ1 imm434/ura3ϻ1 imm434 efg1ϻhisG/efg1ϻhisG-URA3-hisG ura3ϻ1 imm434/ura3ϻ1 imm434 ura3ϻ1 imm434/ura3ϻ1 imm434 ura3ϻ1 imm434/ura3ϻ1 imm434 ADE2/ade2ϻPCK1p-TEC1-URA3 efg1ϻhisG/efg1ϻhisG ura3ϻ1 imm434/ura3ϻ1 imm434 ADE2/ade2ϻPCK1p-TEC1-URA3 cph1ϻhisG/cph1ϻhisG ura3ϻ1 imm434/ura3ϻ1 imm434 ADE2/ade2ϻPCK1p-CPH1-URA3
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
