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A computational model for regulation of nanoscale glucan exposure in Candida albicans

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  • Michael J Wester
  • Jia Lin
  • Aaron K Neumann

Abstract

Candida albicans is a virulent human opportunistic pathogen. It evades innate immune surveillance by masking an immunogenic cell wall polysaccharide, β-glucan, from recognition by the immunoreceptor Dectin-1. Glucan unmasking by the antifungal drug caspofungin leads to changes in the nanostructure of glucan exposure accessible to Dectin-1. The physical mechanism that regulates glucan exposure is poorly understood, but it controls the nanobiology of fungal pathogen recognition. We created computational models to simulate hypothetical physical processes of unmasking glucan in a biologically realistic distribution of cell wall glucan fibrils. We tested the predicted glucan exposure nanostructural features arising from these models against experimentally measured values. A completely spatially random unmasking process, reflective of random environmental damage to the cell wall, cannot account for experimental observations of glucan unmasking. However, the introduction of partially edge biased unmasking processes, consistent with an unmasking contribution from active, local remodeling at glucan exposure sites, produces markedly more accurate predictions of experimentally observed glucan nanoexposures in untreated and caspofungin-treated yeast. These findings suggest a model of glucan unmasking wherein cell wall remodeling processes in the local nanoscale neighborhood of glucan exposure sites are an important contributor to the physical process of drug-induced glucan unmasking in C. albicans.

Suggested Citation

  • Michael J Wester & Jia Lin & Aaron K Neumann, 2017. "A computational model for regulation of nanoscale glucan exposure in Candida albicans," PLOS ONE, Public Library of Science, vol. 12(12), pages 1-20, December.
  • Handle: RePEc:plo:pone00:0188599
    DOI: 10.1371/journal.pone.0188599
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    References listed on IDEAS

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    1. Jacques Banchereau & Ralph M. Steinman, 1998. "Dendritic cells and the control of immunity," Nature, Nature, vol. 392(6673), pages 245-252, March.
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