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

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.

The demise of the Beothuk as a past still present

This article aims to investigate contemporary cultural representations of the Beothuk Indians in art, literature and museum displays in Newfoundland, Canada, focussing on ways these reimagine the past for the present, offering perspectives on contested histories, such as the circumstances leading to the demise of the Beothuk. Wiped out through the impact of colonialism, the Beothuk are the ‘absent other’ who continue to be remembered and made present through the creative arts, largely at the expense of other indigenous groups on the island. Rather than focussing on the ‘non-absent past, according to Polish scholar Ewa Domańska, ‘instead we turn to a past that is somehow still present, that will not go away or, rather, that of which we cannot rid ourselves’ (2006, 346). Depictions of the last Beothuk are part of a cultural remembering where guilt and reconciliation are played out through media of the imagination