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Post transcriptional regulation in pseudomonas-host interactions


Pseudomonas aeruginosa is a common environmental Gram-negative bacillus, which can cause serious infections in immuno-compromised hosts and is the predominant pathogen associated with morbidity and mortality of cystic fibrosis (CF) patients. The pathogenicity of P. aeruginosa is multifactorial and involves: successful adaptation in different environments niches, the production of disease-causing secondary metabolites and virulence factors, motility and the production and delivery of effector toxins into the cytosol of host cells via the TTSS (Type Three Secretion System). P. aeruginosa is also intrinsically resistant to a broad range of antimicrobial agents.

RsmA is a posttranscriptional regulatory protein in P. aeruginosa that works in tandem with a small no n-coding regulatory RNA molecule, RsmB (RsmZ) to regulate the expression of several virulence related genes, including quorum sensing and secondary metabolites. Recently we have compared the transcriptome profiles of P. aeruginosa PAO1 and an isogenic rsmA mutant to study the full impact of RsmA on cellular activities and studied the role of RsmA in microbial-host interactions. Results demponstrated that RsmA altered the expression of genes involved in a variety of pathways and systems important for virulence, including the formation of multi-drug efflux pumps and that during interaction with airway epithelial cells RsmA positively regulated the expression of key regulators of the TTSS.

However, as RsmA is a post-transcriptional regulator, all of these observed effects cannot be explained through the established regulatory mechanisms of RsmA. Therefore, the proposed project involves recruiting a senior researcher (5yrs postgraduate experience) to relocate from Switzerland to Ireland and utilise platform technologies in molecular biology, including Genomics and Protemics, to identify and characterize direct targets of RsmA regulation with regard to virulence and Pseudomonas - host interactions.

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