Interaction of Candida albicans with murine gastrointestinal mucosa from methotrexate and 5-fluorouracil treated animals: in vitro adhesion and prevention

Abstract

The aim of the present study was to investigate whether the cytotoxic anti-cancer drugs methotrexate (MTX) or 5-fluorouracil (5FU), which affect the gastrointestinal (GI) mucosa, would also affect the ability of the damaged mucosa to bind the GI commensal yeast Candida albicans. ICR conventional female mice were treated with intraperitoneal (IP) MTX (3 mg per mouse, or intravenous (IV) 5FU (200 mg kg-1 body weight). On various days post-treatment, the small intestine was removed, tissue disks prepared and exposed for 2 h to radiolabeled C. albicans. The percent adherence of the fungus to the mucosa was assayed by determining the counts per minute (c.p.m.). An increase in the in vitro adherence of C. albicans to murine GI mucosa was found posttreatment with MTX or 5FU. The maximal increase (net increase of 40-50%) was observed on days 3-4 post-treatment with MTX or 5FU, concurrently with the maximal decrease in the total number of white blood cells (WBC) and loss in spleen weight of the treated animals (indicators of cytotoxicity of these drugs). In addition, experiments to block Candida adherence with chitin soluble extract (CSE), an inhibitor used in previous studies, were also carried out. CSE inhibited the adherence of C. albicans to the damaged GI mucosa, as well as to the GI mucosa from normal untreated mice, by up to 64% approximately. Based on these results and on findings from our previous study investigating the adherence of C. albicans to GI mucosa from irradiated mice, it can be concluded that increased adherence of C. albicans to the GI mucosa may occur in patients post-anti-cancer therapy (irradiation, or chemotherapy). This observation may partially explain the high tendency of these debilitated patients to develop systemic candidosis. Further experiments to study adherence of C. albicans to gut mucosa in vivo and eventually to inhibit this adherence with CSE are currently in progress in our laboratory.