Antimicrobial peptide MUC7 12-mer activates the calcium/calcineurin pathway in Candida albicans.
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 muM peptide and grown until an OD(600 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.
Lis
Maciej
M
Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York 14214, USA.
Liu
Teresa T
TT
Barker
Katherine S
KS
Rogers
P David
PD
Bobek
Libuse A
LA
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D009077:Mucins / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D023181:Antimicrobial Cationic Peptides; C083238:MUC7 protein, human; D009077:Mucins; D012471:Salivary Proteins and Peptides; D019703:Calcineurin; D002118:Calcium