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.
MeSH Terms
Acute Disease
Adolescent
Adult
Antibodies, Bacterial/analysis,immunology
Antibody Specificity
Autopsy
Burkholderia Infections/complications,immunology,microbiology
Burkholderia cepacia/immunology,isolation & purification
Chronic Disease
Cystic Fibrosis/complications,immunology,microbiology
Drug Resistance, Microbial
Female
Humans
Lung/immunology,microbiology,pathology
Lung Transplantation
Male
Pneumonia, Bacterial/microbiology
Pseudomonas aeruginosa/immunology,isolation & purification
Sepsis/microbiology
Tissue Distribution
Transplantation, Homologous
Chemicals
Antibodies, Bacterial
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Sajjan Umadevi
Corey Mary
Department of Structural Biology and Biochemistry, *Department of Population Health Sciences, Hospital for Sick Children, †Department of Medicine, Toronto General Hospital, ‡Division of Respiratory Medicine, St Michael's Hospital and §Department of Pediatric Laboratory Medicine and Division of Pathology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Humar Atul
Department of Structural Biology and Biochemistry, *Department of Population Health Sciences, Hospital for Sick Children, †Department of Medicine, Toronto General Hospital, ‡Division of Respiratory Medicine, St Michael's Hospital and §Department of Pediatric Laboratory Medicine and Division of Pathology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Tullis Elizabeth
Department of Structural Biology and Biochemistry, *Department of Population Health Sciences, Hospital for Sick Children, †Department of Medicine, Toronto General Hospital, ‡Division of Respiratory Medicine, St Michael's Hospital and §Department of Pediatric Laboratory Medicine and Division of Pathology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Cutz Ernest
Department of Structural Biology and Biochemistry, *Department of Population Health Sciences, Hospital for Sick Children, †Department of Medicine, Toronto General Hospital, ‡Division of Respiratory Medicine, St Michael's Hospital and §Department of Pediatric Laboratory Medicine and Division of Pathology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Ackerley Cameron
Department of Structural Biology and Biochemistry, *Department of Population Health Sciences, Hospital for Sick Children, †Department of Medicine, Toronto General Hospital, ‡Division of Respiratory Medicine, St Michael's Hospital and §Department of Pediatric Laboratory Medicine and Division of Pathology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Forstner Janet