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Antimicrobial Agents and Chemotherapy, July 2005, p. 2887-2894, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2887-2894.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Efficacy of the Antiadhesin Octyl O-(2-Acetamido-2-Deoxy-ß-D- Galactopyranosyl)-(1-4)-2-O-Propyl-ß-D-Galactopyranoside (Fimbrigal-P) in a Rat Oral Candidiasis Model

M. Foldvari,1* M. R. Jaafari,1,{dagger} J. Radhi,2 and D. Segal3

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada,1 Department of Pathology, McMaster University, Hamilton, Ontario, Canada,2 Helix BioPharma Corp., Aurora, Ontario, Canada3

Received 5 May 2004/ Returned for modification 11 July 2004/ Accepted 16 January 2005

Adherence of Candida albicans to buccal epithelial cells via its fimbrial subunit requires the minimal disaccharide sequence ß-GalNAc(1-4)-ß-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-ß-D-galactopyranosyl)-(1-4)-2-O-propyl-ß-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 premixing 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 ß-GalNAc(1-4)-ß-galactosidase disaccharide to establish adherence.

* Corresponding author. Mailing address: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5C9, Canada. Phone: (306) 966-6338. Fax: (306) 966-6377. E-mail: foldvari{at}duke.usask.ca.

{dagger} Present address: School of Pharmacy and Bu-Ali Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Antimicrobial Agents and Chemotherapy, July 2005, p. 2887-2894, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2887-2894.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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