The cases discussed highlight the main features of familial tumoral calcinosis and indicate the need for improved clinical guidance on the investigations, treatment and genetic screening of familial tumoral calcinosis.

No abstract

Objectives: Small colony variants (SCVs) of Pseudomonas aeruginosa are often isolated in CF that shows a number of changes favouring chronic colonisation. In a murine model of chronic pulmonary colonisation with P. aeruginosa, a phenotypically stable SCV arose during the course of infection. We characterised the genomic and transcriptomic characteristics of the SCV compared to the parent strain, to establish the mechanism behind the switch to the SCV phenotype. Methods: The SCV arose within three days of colonisation. Genomic and transcriptomic analysis was performed by Illumina sequencing. Results: The SCV showed a highly stable phenotype on repeated subculture. Analysis showed typical SCV colony morphology with markedly increased biofilm production. Pulsed field gel electrophoresis showed no difference between parent NH strain and the SCV. DNA sequencing revealed few consistent changes between the parent and SCV other than a single nucleotide mutation within the algD gene. Initial RNA-seq transcriptomic analysis suggests differential expression of over 400 genes, almost all upregulated in the SCV, and many involved in adaptations to adverse environments. These included homologues of the Psl locus involved in biofilm formation, a hyperosmolar-induced protein, and EF-Tu, a bacterial ligand for the platelet activating receptor, important in epithelial adhesion. Conclusion: The heritable change in the SCV responsible for its phenotype remains obscure but may involve epigenetic change which we are investigating with PacBio TM sequencing. The observed upregulated genes give insight into the adaptations required for bacterial survival within the CF lung that could be novel therapeutic targets.