Entry of Burkholderia organisms into respiratory epithelium: CFTR, microfilament and microtubule dependence

Background: The pathogenesis of infection with Burkholderia cepacia complex (Bee) organisms may be linked to its capacity to invade respiratory epithelium. Methods: An antibiotic exclusion assay was used to study B. dolosa AU4459 and B. cenocepacia J2315 invasion into wild-type (WT) and CFTR-deficient respiratory epithelial cells. Inhibitors were used to evaluate Bee invasion dependency on host micro tubule (mt) and microfilament(mf) systems. Results: B. dolosa entered WT-CFTR cells with 5-fold greater efficiency than CFTR deficient cells (25% vs 5%, respectively). Invasion dropped to < 0.5% after either mf or nit inhibition. B. cenocepacia entered WT (0.05%) and CFTR-deficient cells (0.07%) with similarly low efficiencies, which significantly decreased with either mf or nit inhibition (0.008% and 0.002%, respectively). Conclusion: B. dolosa and B. cenocepacia enter respiratory epithelial cells in a mf and nit dependent fashion. Mutated CFTR leads to less internalization of B. dolosa, but not B. cenocepacia. (C) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.