An investigtion of the polymicrobial nature of lower respiratory tract infections in cystic fibrosis patients

Nelson, Andrew (2011) An investigtion of the polymicrobial nature of lower respiratory tract infections in cystic fibrosis patients. Doctoral thesis, Northumbria University.

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Abstract

Cystic fibrosis (CF) is a genetically inherited condition most prevalent amongst Caucasians. In previous studies, it has been demonstrated that bacterial, fungal and viral pathogens cause lung function decline and ultimately result in death due to respiratory failure. Patients with CF produce sputum daily, which makes it an ideal infection to study in terms of access to samples. However, it is unknown how transport of the samples from the patient to the laboratory will affect the results of molecular microbiological analysis. We found that the bacterial community profiles were significantly different in samples stored at room temperature from those which were refrigerated. Furthermore, a significant increase in bacterial load and numbers of Pseudomonas spp. and a significant decrease in number of H. influenzae were seen in the samples stored at room temperature.
In this study we also aimed to characterise the factors which have an effect on the bacterial and fungal communities present in the CF lung in patients who possessed the F508del CFTR allele. We found that gender was a significant factor in the assembly of bacterial communities, due to a reduction in bacterial diversity and community evenness. Furthermore, we identified that P. aeruginosa colonisation affected bacterial community composition. We have also identified that bacterial community assembly in the CF lung appears to be stochastic. However, our data also shows that gender and P. aeruginosa colonisation affect assembly suggesting that, in some respects, a deterministic community assembly is also being observed. Our data also suggests that fungal communities are more diverse than is currently recognised.
Additionally, we have found that patients who are homozygous for the F508del CFTR mutation harbour more rich fungal communities than patients who are heterozygous.
A further objective was to follow these patients longitudinally to determine the stability of the CF lung microbiota, to determine the effects of antibiotic therapy, and to assess if any changes occurred in the CF lung during times of pulmonary exacerbation which could be identified as the causative agent. We did not find a significant relationship between exacerbations and the bacterial communities present in CF. However, in one patient we found that a particular bacterial taxa was present when the patient presented with an exacerbation but was absent when the patient was stable, suggesting that acquisition of a new bacterial taxa can potentially cause an exacerbation. We also found that an increase in bacterial load was not the cause of exacerbations in our cohort. Furthermore, the presence and abundance of fungal species was found not to be the cause of exacerbations.

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