Characterising novel virulence mechanisms in the emerging hospital-acquired pathogen; Acinetobacter baumannii

Characterising novel virulence mechanisms in the emerging hospital-acquired pathogen; Acinetobacter baumannii (A/Professor John Boyce, Dr Faye Morris and and Professor Anton Peleg) Small RNA (sRNA) molecules play important roles in the regulation of a wide range of bacterial phenotypes including virulence. Together with Dr. Gerald Murray we have previously determined which A. baumannii sRNA molecules are expressed in vivo during a mouse infection model. We predict that sRNAs expressed at high levels in vivo will have a role in regulating A. baumannii virulence factors. We have generated an assortment of individual sRNA mutants and in this project we will select those that are highly expressed in vivo and complement the mutants by generating individual constructs expressing the relevant sRNA from different promoters. By comparing our repertoire of strains (ie sRNA mutants, complements and overexpression strains) we will analyse the effects on a range of virulence associated phenotypes (growth in human serum, biofilm formation, and mouse infection models), with a view to identify and confirm the sRNA specific targets using high- throughput proteomics and RNA sequencing of sRNA- mRNA duplexes. Where inactivation of an sRNA affects virulence we will design and construct sRNA inhibitors and test these as novel antimicrobials.