Antimicrobial peptide MUC7 12-mer activates the calcium/calcineurin pathway in Candida albicans

Authors

  • Maciej Lis,

    1. Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York, USA
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  • Teresa T. Liu,

    1. Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Centre, Memphis, TN, USA
    2. Le Bonheur Children's Medical Centre, Children's Foundation Research Centre, Memphis, TN, USA
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  • Katherine S. Barker,

    1. Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Centre, Memphis, TN, USA
    2. Le Bonheur Children's Medical Centre, Children's Foundation Research Centre, Memphis, TN, USA
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  • P. David Rogers,

    1. Department of Pharmacy, College of Pharmacy, University of Tennessee Health Science Centre, Memphis, TN, USA
    2. Le Bonheur Children's Medical Centre, Children's Foundation Research Centre, Memphis, TN, USA
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  • Libuse A. Bobek

    1. Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York, USA
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  • Editor: Richard Calderone

  • Present address: Teresa T. Liu, Department of Biological Sciences, Mellon Institute, Carnegie Mellon University, 4400 Fifth Ave, Pittsburgh, PA 15213, USA.

Correspondence: Libuse A. Bobek, Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York 14214, USA. Tel.: +1 716 829 2465; fax: +1 716 829 3942; e-mail: lbobek@buffalo.edu

Abstract

MUC7 12-mer is a cationic antimicrobial peptide derived from the N-terminal region of human low-molecular-weight salivary mucin. In order to gain new insights into the modes of action of the 12-mer against opportunistic fungal pathogen Candida albicans, we examined changes in the gene expression profile of C. albicans upon exposure to this peptide. Cells at an early logarithmic phase were exposed to 6 μM peptide and grown until an OD600 nm of approximately 0.4 was reached. Changes in gene expression were determined by microarray analysis and showed that 19 out of the total of 531 genes, whose expression was elevated in response to the peptide, are regulated by the calcium/calcineurin signalling pathway. Inactivation of this pathway by deletions, or by FK506, caused hypersensitivity to the peptide, demonstrating the importance of this pathway to the defense of C. albicans against the MUC7 peptide. Other differentially expressed genes that were detected include those encoding subunits of proteasome, and genes involved in cell stress, iron metabolism, cell wall maintenance and small-molecule transport. The presented results suggest that the calcium/calcineurin signalling pathway plays a role in the adaptation of C. albicans to the MUC7 antimicrobial peptide.

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