Adherence of Burkholderia cepacia to respiratory tract epithelial cells and inhibition with dextrans

Abstract

Adherence of Burkholderia cepacia to cells of the respiratory tract of patients with cystic fibrosis (CF) appears to be a necessary precondition for colonization and infection. To date, no effective anti-adhesive strategy has been devised for preventing B. cepacia infection in CF patients. It was found in this study that B. cepacia adhered to respiratory epithelial cells both in vitro and in vivo. However, strains with cable-like pili (Cbl) exhibited the typical clump formation on pneumocytes, whereas non-cable piliated strains predominantly showed single-cell adherence. Dextrans (nominally 4000-10000 Da) significantly inhibited adhesion of B. cepacia to A549 pneumocytes. When compared on an equal weight basis, the nominally 10000 Da dextran was most inhibitory. A dose-dependent inhibitory effect (up to 80 mg ml(-1)) was observed for most strains. Dextran exerted less of an anti-adhesive effect on the two Cbl+ strains than on the others which were Cbl-. Dextrans appeared to block the adherence in a non-specific fashion, as shown by the observations that the inhibitory effect was readily reversible and oligosaccharides composed of 2-4 glucose units with the same alpha-1,6 linkage were not inhibitory. The mean molecular masses of dextrans used in this study, as determined by gel filtration and MS, were approximately 10-fold lower than those indicated by the manufacturers. Our data suggest that dextran of nominal molecular mass 4000 Da at a concentration of 40 mg ml(-1) (10 mM according to manufacturer's quoted molecular mass) or more may be useful in patients with CF to prevent colonization and infection with B. cepacia.