Immunolocalisation of Burkholderia cepacia in the lungs of cystic fibrosis patients.

Abstract

Infection by Burkholderia cepacia is sometimes fatal in patients with cystic fibrosis (CF), as the organism can cause necrotising pneumonia and septicaemia (the cepacia syndrome), and is resistant to antibiotics. To increase knowledge of the pathogenesis of lung infection, the present study investigated the distribution of B. cepacia in lung explants from nine CF recipients of double lung transplants, of which six were colonised with both B. cepacia and Pseudomonas aeruginosa and the other three with P. aeruginosa only. In one case, explants of the donor lung (allograft) became available after the patient succumbed post-operatively to the cepacia syndrome. Further autopsy sections were examined from two patients who had chronic and then acute infection with B. cepacia. A specific antibody reactive with all five genomovars of the B. cepacia complex and another antibody specific for the 22-kDa adhesin of cable pili, were used to localise bacteria in situ. In chronic infection, the organisms were diffusely distributed, but most concentrated in hyperplastic bronchiolar epithelium, inflamed peribronchial and perivascular areas, between adjacent airway epithelial cells and in pathologically thickened alveolar septae and luminal macrophages. In acute infections the distribution was more focal, with B. cepacia on injured airway surfaces and in sites of pneumonia and abscess formation. In autopsy sections from one of the patients with chronic, then acute infection, B. cepacia was also observed in the lumen of blood capillaries. These results suggest that B. cepacia has the capacity to be highly invasive, migrating from the airways across the epithelial barrier to invade the lung parenchyma and capillaries, thereby initiating septicaemia.