Exploring the activity of novel virulence regulators in the hospital pathogen Acinetobacter baumannii

Polysaccharide capsule is a critical virulence factor in many bacteria, including the priority drug-resistant pathogen Acinetobacter baumannii. The capsule is the first part of the bacterium “seen” by the host and is therefore a key mediator of immune interactions, and a potential target for novel drugs. Despite its importance for infection, very little is known about how production of capsule is coordinated and controlled in this species. We have performed the first genome-scale screen for genes influencing capsule production or retention in two strains of A. baumannii. The results indicate a complex regulation network linked to various environmental cues. Several novel capsule regulators were identified, including some not previously linked to capsule or virulence in any bacterial species. This project will examine the activity of one to two novel regulators of capsule in detail, to define their full range of phenotypic effects. The transcriptional targets will be defined by RNA sequencing of wild-type and mutant A. baumannii. Results will be analysed against the diversity of the A. baumannii population to determine whether the activity is species-wide or specific to a particular clade of this pathogen.