The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung

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dc.contributor.advisor Ryan, Robert P. en
dc.contributor.advisor Dow, Max en Twomey, Kate B. 2015-06-19T10:47:28Z 2014 2014
dc.identifier.citation Twomey, K. B. 2014. The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung. PhD Thesis, University College Cork. en
dc.description.abstract There is an increasing appreciation of the polymicrobial nature of bacterial infections associated with Cystic Fibrosis (CF) and of the important role for interactions in influencing bacterial virulence and response to therapy. Patients with CF are co-infected with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are cis-2-unsaturated fatty acids. Previous studies showed that DSF from S. maltophilia leads to altered biofilm formation and increased tolerance to antibiotics in P. aeruginosa and that these responses require the P. aeruginosa sensor kinase PA1396. The work in this thesis aims of further elucidate the influence and mechanism of DSF signalling on P. aeruginosa and examine the role that such interspecies signalling play in infection of the CF airway. Next generation sequencing technologies targeting the 16S ribosomal RNA gene were applied to DNA and RNA isolated from sputum taken from cohorts of CF and non-CF subjects to characterise the bacterial community. In parallel, metabolomics analysis of sputum provided insight into the environment of the CF airway. This analysis revealed a number of observations including; that differences in metabolites occur in sputum taken from clinically stable CF patients and those with exacerbation and DNA- and RNA-based methods suggested that a strong relationship existed between the abundance of specific strict anaerobes and fluctuations in the level of metabolites during exacerbation. DSF family signals were also detected in the sputum and a correlation with the presence of DSFproducing organisms was observed. To examine the signal transduction mechanisms used by P. aeruginosa, bioinformatics with site directed mutagenesis were employed to identify signalling partners for PA1396. A pathway suggesting a role for a number of proteins in the regulation of several factors following DSF recognition by PA1396 were observed. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Kate B. Twomey. en
dc.rights.uri en
dc.subject Polymicrobial Infection en
dc.subject Pseudomonas aeruginosa en
dc.subject Interspecies signalling en
dc.subject Cystic fibrosis en
dc.title The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text not available en Indefinite en 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en Microbiology en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.embargoformat Not applicable en
dc.internal.conferring Summer Conferring 2014

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© 2014, Kate B. Twomey. Except where otherwise noted, this item's license is described as © 2014, Kate B. Twomey.
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