Inhibition of adherence and killing of Candida albicans with a 23-Mer peptide (Fn/23) with dual antifungal properties.
Candida albicans adheres to host tissue and then proliferates in order to establish a commensal as well as a pathogenic state. Specific adherence to proteins is provided by several surface adhesins of Candida. Two well-studied proteins, Als1p and Als5p, do not require energy for adherence to occur (dead as well as living cells adhere) and have a multiplier effect of cell-cell aggregation that mediates the formation of microcolonies of Candida cells. The entire process is spontaneous, reversible, and stable for physiologically relevant chemical and physical forces. This adherence process is inhibited by the addition of free peptide ligands, including a 23-mer derived from fibronectin (Fn/23) that binds to the adhesins through H bond formation. Adherence was measured by determining the number of yeast cells that adhered to 90-microm-diameter polyethylene glycol (PEG) beads with a 7-mer peptide (KLRIPSV) synthesized on the surfaces of the beads. The concentration of the Fn/23 peptide that inhibited the adherence of cells to the peptide-coated beads by 50% was 4 to 5 microM, and the magnitudes of adherence were similar regardless of the presence or absence of physiologic salt concentrations. The minimum fungicidal concentration of Fn/23 was 2 to 4 microM in water, but there was no killing in physiologic salt concentrations. Peptides from the C and N termini or the center sequence of Fn/23 had no effect on inhibition of adherence and little effect on fungal viability. The fungicidal effect was similar to that seen with 23-, 19-, and 18-mer peptides derived from porcine myeloid cells, a Helicobacter pylori ribosomal protein, and a hybrid of cecropin and magainin, respectively. However, these fungicidal peptides did not inhibit C. albicans adherence to the peptide-coated PEG beads. This dual property of Fn/23, i.e., inhibition of adherence and killing of C. albicans, may provide important adjuvant effects in the treatment of disease caused by this fungus.
Klotz
Stephen A
SA
Section of Infectious Diseases, Department of Medicine, University of Arizona, 1501 N. Campbell Ave., Tucson, AZ 85724, USA. sklotz@u.arizona.edu
Gaur
Nand K
NK
Rauceo
Jason
J
Lake
Douglas F
DF
Park
Y
Y
Hahm
K S
KS
Lipke
Peter N
PN
D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000378:metabolism* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism* / Q000494:pharmacology*; D002021:Buffers; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D003470:Culture Media; D005353:Fibronectins / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D012269:Ribosomal Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D013552:Swine
D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D002021:Buffers; D003470:Culture Media; D005353:Fibronectins; C494143:Fn-23 peptide; D010455:Peptides; D012269:Ribosomal Proteins; C086301:porcine myeloid antibacterial peptide 23