Inhibition of Burkholderia multivorans adhesion to lung epithelial cells by bivalent lactosides

Abstract

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a real-time PCR method to quantify the levels of binding of B. multivorans to the lung epithelial cells, we have examined glycoconjugate derivatives for their potential to inhibit host cell attachment. Bivalent lactosides previously shown to inhibit galectin binding significantly reduced the attachment of B. multivorans to CF lung epithelial cells at micromolar concentrations. This was in contrast to monosaccharides and lactose, which were only effective in the millimolar range. Development of glycoconjugate therapies such as these, which inhibit attachment to lung epithelial cells, represent an alternative means of preventing infection with inherently antimicrobially resistant pathogens such as B. multivorans.

Figure 1

Chemical structure of bivalent lactosides used in this study. (a) RL1; (b) RL2 and (c) RL5.

Figure 2

Inhibition of binding of B. multivorans to lung epithelial cells. Bacteria were pre-incubated with lactosides for 30 min prior to infection of lung epithelial cells. Bars represent the fold change in binding of bacteria to lung epithelial cells relative to uninhibited solvent control.