Efficacy of the antiadhesin octyl O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl)-(1-4)-2-O-propyl-beta-D-galactopyranoside (Fimbrigal-P) in a rat oral candidiasis model.
Adherence of Candida albicans to buccal epithelial cells via its fimbrial subunit requires the minimal disaccharide sequence beta-GalNAc(1-4)-beta-galactosidase in host cell receptors asialo-GM1 or asialo-GM2. This and other disaccharides and some of its synthetic derivatives have been shown to inhibit purified fimbrial or pathogen binding in vitro. This study evaluates the in vivo efficacy of the propyl derivative of this disaccharide, octyl O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl)-(1-4)-2-O-propyl-beta-D-galactopyranoside, or Fimbrigal-P, incorporated into a mucoadhesive polymer formulation in a rat oral candidiasis model. Colony counts of microcurette samples from the oral cavity and tongue homogenates were used to estimate the effectiveness of four treatment modalities to reduce oral fungal burden. All treatment modalities (preventative, premixing with the Candida inoculant, drinking water, and treatment) significantly reduced fungal burden compared to untreated control animals by day 9; however, the preventative and pre-mixing approaches provided a faster rate of fungal clearance. The low toxicity and immunogenicity of this synthetic carbohydrate and its stability in saliva, as demonstrated by high-performance liquid chromatography, make it a promising candidate for the prevention and treatment of microbial infections in which the pathogen relies on the beta-GalNAc(1-4)-beta-galactosidase disaccharide to establish adherence.
Foldvari
M
M
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. foldvari@duke.usask.ca
Jaafari
M R
MR
Radhi
J
J
Segal
D
D
D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D002180:Candidiasis, Oral / Q000188:drug therapy* / Q000382:microbiology; D002448:Cell Adhesion / Q000187:drug effects; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000737:chemistry; D014059:Tongue / Q000382:microbiology*; D016896:Treatment Outcome
D004187:Disaccharides; D005656:Fungal Proteins; D011108:Polymers; C097786:galactopyranosyl-(1-1)-galactopyranoside