Effect of an arginine-glycine-aspartic acid-containing peptide on hematogenous candidal infections in rabbits.
The adherence of Candida albicans yeast cells to the subendothelial extracellular matrix, fibronectin, laminin, and type I and IV collagen was tested. Fibronectin (10(-7) M) and a peptide, PepTite-2000 (Telios Pharmaceuticals Inc., San Diego, Calif.), containing the sequence arginine-glycine-aspartic acid (RGD) inhibited Candida adherence to these targets by greater than 90%. When C. albicans was perfused over ex vivo rabbit aortic endothelium, there was no significant difference in the amount of adherence in the presence or absence of the RGD-containing peptide. However, the RGD-containing peptide reduced the number of Candida organisms present in liver, brain, heart, and kidneys (P less than 0.05) of rabbits 4 h after intravenous inoculation of 5 x 10(7) C. albicans yeast cells. The peptide also reduced the number of macroscopic Candida abscesses in the kidneys of rabbits 72 h after intravenous inoculation of 10(7) C. albicans yeast cells (P less than 0.05). Inhibition of Candida adherence in vitro and in vivo may occur because the peptide blocks a fungal receptor that is necessary for adherence.
Klotz
S A
SA
Kansas University School of Medicine, Kansas City 66160.
Smith
R L
RL
Stewart
B W
BW
D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects / Q000382:microbiology; D005260:Female; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000382:microbiology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits
D005353:Fibronectins; D010455:Peptides; D003094:Collagen