Abstract
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.
Highlights
The cell surface has two pivotal roles in the survival of microorganisms: protection and interaction
There was a strikingly expanded role for C. albicans protein kinases (PKs) in cell wall regulation (CWR): 24 of the 80 mutants were hypersensitive to the cell wall inhibitor caspofungin, compared to 10 of the mutants that were predicted by model organism studies (Table 1)
Our most striking result is that C. albicans CWR relies upon conserved PKs with novel functions compared to their orthologs, representing an expansion of the circuitry involved in this process (Fig. 5)
Summary
The cell surface has two pivotal roles in the survival of microorganisms: protection and interaction. The interactive role includes both sensing of external signals and binding to other cells or external surfaces [3,4]. These two functions necessitate a delicate balance for organisms that can adapt to diverse niches: protection is accomplished by a rigid and impermeable surface; interaction is accomplished by a dynamic one. It is a commensal microbe that is acquired soon after birth, and occupies both the GI and GU tracts. These colonization sites represent distinct environments in terms of cohabitant microbiota, pH, and nutrients. C. albicans is the major fungal commensal and the major fungal pathogen of humans
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