An extensive circuitry for cell wall regulation in Candida albicans.
An extensive circuitry for cell wall regulation in Candida albicans.
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DOI:
10.1371/journal.ppat.1000752
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发表时间:
2010-02-05
期刊:
影响因子:
6.7
通讯作者:
Mitchell AP
中科院分区:
文献类型:
--
作者:
Blankenship JR;Fanning S;Hamaker JJ;Mitchell AP
Protein kinases play key roles in signaling and response to changes in the external environment. The ability of Candida albicans to quickly sense and respond to changes in its environment is key to its survival in the human host. Our guiding hypothesis was that creating and screening a set of protein kinase mutant strains would reveal signaling pathways that mediate stress response in C. albicans. A library of protein kinase mutant strains was created and screened for sensitivity to a variety of stresses. For the majority of stresses tested, stress response was largely conserved between C. albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. However, we identified eight protein kinases whose roles in cell wall regulation (CWR) were not expected from functions of their orthologs in the model fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe. Analysis of the conserved roles of these protein kinases indicates that establishment of cell polarity is critical for CWR. In addition, we found that septins, crucial to budding, are both important for surviving and are mislocalized by cell wall stress. Our study shows an expanded role for protein kinase signaling in C. albicans cell wall integrity. Our studies suggest that in some cases, this expansion represents a greater importance for certain pathways in cell wall biogenesis. In other cases, it appears that signaling pathways have been rewired for a cell wall integrity response. Candida albicans is the major fungal commensal and pathogen of humans. Like most microorganisms, C. albicans is surrounded and protected by a cell wall. This cell wall has two purposes: to act as a rigid “exoskeleton” to prevent cells from bursting, and to provide a surface where a cell can interact with the outside environment while protecting the cell itself from this environment. Maintenance of this structure has been well studied in the model fungus, Saccharomyces cerevisiae, but previous evidence suggested that C. albicans might have additional inputs to this process. By creating and testing a library of mutant strains for sensitivity to cell wall stress, we were able to identify a number of conserved genes with roles in this process not shared by their S. cerevisiae counterparts. Although some of these genes had previously been linked to cell wall integrity, it appears that they have increased impact on this process in C. albicans. For other genes, their role in cell wall integrity may represent a novel connection. Our findings provide insight into novel aspects of cell wall integrity in this pathogen and lay a foundation for its more detailed analysis.
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影响因子:
7.8
作者:
Delley, P A;Hall, M N
通讯作者:
Hall, M N
影响因子:
--
作者:
Bimbó, A;Jia, YH;Liu, JH
通讯作者:
Liu, JH
DOI:
10.1038/nrmicro1960
发表时间:
2008-09
期刊:
Nature reviews. Microbiology
影响因子:
--
作者:
通讯作者:
--
影响因子:
5.3
作者:
Bidlingmaier, S;Weiss, EL;Snyder, M
通讯作者:
Snyder, M
DOI:
10.1073/pnas.93.23.13223
发表时间:
1996-11-12
影响因子:
11.1
作者:
Kohler, JR;Fink, GR
通讯作者:
Fink, GR