Creation of a genomic Candida albicans library to study resistance and susceptibility to cationic antimicrobial peptides

Susceptibility and resistance to antimicrobial peptides has become an area of increased interest given the emergence of microbial pathogens that are resistant to a broad array of conventional anti-infective agents. An example is the fungal pathogen, Candida albicans, which exhibits increased frequency in life-threatening infections, yet reduced susceptibility to available anti-fungal agents. Studies were undertaken to identify the gene or genes in a strain of Candida albicans resistant to antimicrobial peptides. The strategy utilized vector-mediated expression of candidal genes in the bacterial organism Escherichia coli (E. coli). Escherichia coli transformed with genomic DNA from the peptide resistant Candida albicans strain were then screened to assess acquired resistance to protamine, a prototype antimicrobial peptide. Protamine resistant mutants were found; however the clones were shown to be spontaneous mutants. No Candida albicans genes conferring protamine resistance were identified. Thus, Candida albicans may employ multi-factorial and/or non-genetic mechanisms as a basis for resistance to protamine or other antimicrobial peptides.