1887

Abstract

Chitin is an essential structural polysaccharide component of the cell walls of fungi. Because chitin is not found in human cells it also represents an attractive target for antifungal therapy. Recent reports have suggested that cells can resist killing by the antifungal echinocandin both and by up-regulating chitin synthesis and thereby sustaining cell wall integrity (Lee , 2012). However, when echinocandins are removed, the chitin content quickly returns to basal levels, suggesting that elevated chitin cell wall content represents a fitness cost. We show here that those cells that die in the presence of echinocandins often have supra-high rather than high chitin levels, and therefore having too much chitin in the cell wall may be detrimental for viability. Furthermore, mutants in the Ca/calcineurin pathway are associated with appearance of viable super-high chitin cells following cell wall stress, suggesting suggest that this pathway may negatively regulate other chitin stimulation pathways. We, therefore, propose that has evolved a mechanism to maintain their chitin content high enough to protect cells against cell wall damage, but not so high that will negatively affect cell viability. In our model, the Ca/calcineurin pathway acts as a buffering system or attenuator in maintaining viable high chitin cells by coordinating both chitin upregulation and modulation of the cell wall integrity pathway, through negative regulation of the MAPK Mkc1 pathway. In summary, we have uncovered a novel mechanism used by to survive cell wall stress imposed by echinocandin treatment.

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/content/journal/acmi/10.1099/acmi.byg2019.po0002
2019-11-01
2019-12-09
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http://instance.metastore.ingenta.com/content/journal/acmi/10.1099/acmi.byg2019.po0002
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