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Bovine pancreatic trypsin inhibitor is a new antifungal peptide that inhibits cellular magnesium uptake
Author(s) -
Bleackley Mark R.,
Hayes Brigitte M.,
Parisi Kathy,
Saiyed Tamana,
Traven Ana,
Potter Ian D.,
Weerden Nicole L.,
Anderson Marilyn A.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12621
Subject(s) - biology , yeast , candida albicans , saccharomyces cerevisiae , biochemistry , trypsin , magnesium , antimicrobial peptides , peptide , mode of action , corpus albicans , growth inhibition , antimicrobial , mechanism of action , microbiology and biotechnology , enzyme , cell growth , in vitro , chemistry , organic chemistry
Summary Antimicrobial peptides ( AMPs ) are promising agents for control of bacterial and fungal infections. Traditionally, AMPs were thought to act through membrane disruption but recent experiments have revealed a diversity of mechanisms. Here we describe a novel antifungal activity for bovine pancreatic trypsin inhibitor ( BPTI ). BPTI has several features in common with a subset of antimicrobial proteins in that it is small, cationic and stabilized by disulphide bonds. BPTI inhibits growth of S accharomyces cerevisiae and the human pathogen C andida albicans . Screening of the yeast heterozygous essential deletion collection identified the magnesium transporter Alr1p as a potential BPTI target. BPTI treatment of wild type cells resulted in a lowering of cellular Mg 2+ levels. Populations treated with BPTI had fewer cells in S ‐phase of the cell cycle and a corresponding increase of cells in G 0 / G 1 and G 2 phases. The same patterns of cell cycle arrest obtained with BPTI were also obtained with the magnesium channel inhibitor hexamine( III )cobalt chloride. Analysis of the growth inhibition of C . albicans revealed that BPTI is inhibiting growth via the same mechanism in the two yeast species. Inhibition of magnesium uptake by BPTI represents a novel mechanism of action for AMPs .