The role of P-glycoprotein and breast cancer resistance protein (BCRP) in bacterial attachment to human gastrointestinal cells.

BACKGROUND AND AIMS Active efflux proteins such as P-glycoprotein (P-gp) are thought to have a protective role in the intestinal tract by preventing xenotoxin absorption. Some bacteria also need to adhere to the intestinal tract before causing disease through adhesin secretion. Thus, this study was initiated to examine whether any association exists between bacterial adhesion. METHODS Three human cell lines (Caco2, RKO, and MCF7), and 6 species of bacteria were used in this study (Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Klebsiella pneumoniae, Clostridium sporogenes and Pseudomonas aeruginosa). Following incubation of our cells with active efflux inhibitors, bacteria incubated with a stable fluorescent dye were co-incubated at 37°C for various times up to 240min. Fluorescence intensity was used to compare bacterial attachment to these cell lines with either normal efflux protein expression or with induction or inhibition of efflux proteins. RESULTS P-gp inhibition by either PSC-833 or GF120918 resulted in a significant increase of all bacterial attachment to Caco2 cells up to 3 fold. RKO cells and MCF7 cells did not alter their bacterial attachment with PSC-833. Fumitremorgen C, a dedicated BCRP inhibitor had no effect. In addition, rifampicin, a P-gp inducer, resulted in some limited reduction in Salmonella and Klebsiella attachment only. CONCLUSIONS These results indicate P-gp expression may contribute to the resistance of potential bacterial toxicity, by preventing them adhering to human enterocytes cells in the gastrointestinal tract, which may reduce the risk or intensity of gastrointestinal disorders.