Secreted aspartic peptidases of Candida albicans liberate bactericidal hemocidins from human hemoglobin.
Secreted aspartic peptidases (Saps) are a group of ten acidic hydrolases considered as key virulence factors of Candida albicans. These enzymes supply the fungus with nutrient amino acids as well as are able to degrade the selected host's proteins involved in the immune defense. Our previous studies showed that the human menstrual discharge is exceptionally rich in bactericidal hemoglobin (Hb) fragments - hemocidins. However, to date, the genesis of such peptides is unclear. The presented study demonstrates that the action of C. albicans isozymes Sap1-Sap6, Sap8 and Sap9, but not Sap7 and Sap10, toward human hemoglobin leads to limited proteolysis of this protein and generates a variety of antimicrobial hemocidins. We have identified these peptides and checked their activity against selected microorganisms representative for human vagina. We have also demonstrated that the process of Hb hydrolysis is most effective at pH 4.0, characteristic for vagina, and the liberated peptides showed pronounced killing activity toward Lactobacillus acidophilus, and to a lower degree, Escherichia coli. However, only a very weak activity toward Staphylococcus aureus and C. albicans was noticed. These findings provide interesting new insights into pathophysiology of human vaginal candidiasis and suggest that C. albicans may be able to compete with the other microorganisms of the same physiological niche using the microbicidal peptides generated from the host protein.
Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Kraków, Poland.
Oliwia
O
Bocheńska
Maria
M
Rąpała-Kozik
Natalia
N
Wolak
Grażyna
G
Braś
Andrzej
A
Kozik
Adam
A
Dubin
Wataru
W
Aoki
Mitsuyoshi
M
Ueda
Paweł
P
Mak
D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000201:enzymology* / Q000472:pathogenicity; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007779:Lactobacillus acidophilus / Q000187:drug effects; D008597:Menstrual Cycle / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D059748:Proteolysis; D014621:Vagina / Q000378:metabolism / Q000382:microbiology
D006454:Hemoglobins; D010446:Peptide Fragments; D010455:Peptides; D016282:Aspartic Acid Endopeptidases
Antibacterial; Bactericidal; Hemocidins; Hemoglobin; Menstruation; Microbicidal; Peptidases; Peptides; Sap; Secreted aspartic peptidases; Vagina