Background Burkholderia cepacia complex (BCC) organisms are important pathogens in Cystic Fibrosis (CF). They infect the CF lung and paranasal sinuses and are resistant to most antibiotics. Lung transplantation is a recognised treatment for CF patients with end stage disease and BCC infections. Lipopolysaccharide (LPS) is an important virulence determinant of Gram negative organisms and the CF epithelium appears to induce host-specific LPS changes in infecting pathogens. We have recently demonstrated CF specific lipid A conformational changes in BCC LPS which are likely to increase resistance to host cationic proteins. Early after lung transplantation pre-transplant organisms are often isolated in the lung lavages of transplanted CF patients probably reflecting infection of the donor lungs from the recipients upper airway. We hypothesized that persisting strains of BCC found in post lung transplant lung lavages may demonstrate conformational change in LPS reflecting the change from a CF to non-CF milieu. Methods We tested paired BCC strains collected from U.K. CF patients transplanted at the Freeman Hospital who had pre-transplant BCC infection and who also had BCC infections present in the post-transplanted lung recovered at routine post operative lavages one week after transplantation. Using PCR techniques we were able to demonstrate the persistence of the pre-transplant strain. This was done initially by demonstrating the same BCC genomovar (sub-species) grouping pre and post transplant using genomovar specific primers and secondly by pulsed field gel electrophoresis using macrorestriction fingerprinting. The lipopolysaccharide from paired isolates were then compared by preparing SDS-gels that were silver stained for LPS. Results We were able to demonstrate the persistence of pre-transplant BCC infecting organisms in 4 patients transplanted at our centre using the above PCR techniques. In these patients there were changes in migration patterns of the LPS when comparing pre and post transplant strains. Conclusions Whilst prior data from our lab and others suggest lipid A and LPS changes are present in organisms isolated from CF airways it has been unclear if these changes remain fixed or are plastic to a changing environment. Our data suggests that this is a dynamic process with LPS changes within one week of transplantation which could be therapeutically useful. Further work assessing changes in the proinflammatory activity of LPS and lipid A conformation extracted from the paired pre and post transplant strains is under way.
University of Newcastle (2004) J Physiol 559P, PC5
Communications: Host epithelium and pathogen lipopolysaccharide interactions; lessons from lung transplantation for Cystic Fibrosis
De Soyza, A; Perry, J; Doherty, C; Gould, K; Govan, JRW; Corris, PA; Khan, CMA;
1. Respiratory Medicine, University Of Newcastle, Newcastle, United Kingdom. 2. Medical Microbiology, Freeman Hospital, Newcastle, United Kingdom. 3. Medical Microbiology, University Of Edinburgh, Edinburgh, United Kingdom. 4. School of Cell and Biosciences, University of Newcastle, Newcastle, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.