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| Title |
Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
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|---|---|
| Published in |
BMC Genomics, July 2016
|
| DOI | 10.1186/s12864-016-2853-5 |
| Pubmed ID | |
| Authors |
Genny Degani, Enrico Ragni, Pedro Botias, Davide Ravasio, Julia Calderon, Elena Pianezzola, Jose Manuel Rodriguez-Peña, Maria Antonietta Vanoni, Javier Arroyo, William A. Fonzi, Laura Popolo |
| Abstract |
The cell wall is essential for the yeast to hypha (Y-H) transition that enables Candida albicans to invade human tissues and evade the immune system. The main constituent, β(1,3)-glucan, is remodeled by glucanosyltransferases of the GH72 family. Phr1p is responsible of glucan remodeling at neutral-alkaline pH and is essential for morphogenesis and virulence. Due to the pH-regulated expression of PHR1, the phr1Δ phenotype is manifested at pH > 6 and its severity increases with the rise in pH. We exploited the pH-conditional nature of a PHR1 null mutant to analyze the impact of glucan remodeling on the hyphal transcriptional program and the role of chitin synthases in the hyphal wall stress (HWS) response. In hyphal growth inducing conditions, phr1Δ germ tubes are defective in elongation, accumulate chitin, and constitutively activate the signaling pathways mediated by the MAP kinases Mkc1p, Cek1p and Hog1p. The transcriptional profiles revealed an increase of transcript levels for genes involved in cell wall formation (CHS2 and CHS8, CRH11, PGA23, orf19.750, RBR1, RBT4, ECM331, PGA6, PGA13), protein N-glycosylation and sorting in the ER (CWH8 and CHS7), signaling (CPP1, SSK2), ion transport (FLC2, YVC1), stress response and metabolism and a reduced expression of adhesins. A transient up-regulation of DNA replication genes associated with entry into S-phase occurred whereas cell-cycle regulating genes (PCL1, PCL2, CCN1, GIN4, DUN1, CDC28) were persistently up-regulated. To test the physiological relevance of altered CHS gene expression, phr1Δ chsxΔ (x = 2,3,8) mutant phenotypes were analyzed during the Y-H transition. PHR1 deletion was synthetic lethal with CHS3 loss on solid M199 medium-pH 7.5 and with CHS8 deletion on solid M199-pH 8. On Spider medium, PHR1 was synthetic lethal with CHS3 or CHS8 at pH 8. The absence of Phr1p triggers an adaptive response aimed to reinforce the hyphal cell wall and restore homeostasis. Chs3p is essential in preserving phr1Δ cell integrity during the Y-H transition. Our findings also unveiled an unanticipated essential role of Chs8p during filamentation on solid media. These results highlight the flexibility of fungal cells in maintaining cell wall integrity and contribute to assessments of glucan remodeling as a target for therapy. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Unknown | 37 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 8 | 21% |
| Student > Ph. D. Student | 6 | 16% |
| Student > Bachelor | 3 | 8% |
| Researcher | 3 | 8% |
| Student > Doctoral Student | 2 | 5% |
| Other | 5 | 13% |
| Unknown | 11 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 21% |
| Immunology and Microbiology | 7 | 18% |
| Biochemistry, Genetics and Molecular Biology | 6 | 16% |
| Economics, Econometrics and Finance | 1 | 3% |
| Psychology | 1 | 3% |
| Other | 2 | 5% |
| Unknown | 13 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 August 2016.
All research outputs
#14,857,184
of 22,880,691 outputs
Outputs from BMC Genomics
#6,147
of 10,666 outputs
Outputs of similar age
#212,124
of 350,782 outputs
Outputs of similar age from BMC Genomics
#129
of 223 outputs
Altmetric has tracked 22,880,691 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 10,666 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
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We're also able to compare this research output to 223 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.