Grant: Doctoral: Vanier Canada Graduate Scholarships

Effective antimicrobial agents are essential for treatment of life-threatening bacterial infections. Although bacteria develop resistance to therapies naturally by mutagenesis, emergence of resistant strains is accelerating because of irresponsible antibiotic use. Pseudomonas aeruginosa is a highly adaptable species of bacteria that is listed amongst the most threatening drug-resistant pathogens for which new antibiotics are urgently needed. The display of adaptive phenotypes, including biofilm formation and rapid surface propagation, are associated with increased resistance and are hallmarks of bacterial stress responses that allow coping with nutrient limitation and antibiotic exposure in the host. These adaptive lifestyles may be regulated by the expression of genes that are responsible for sensing and responding to environmental stimuli via central metabolism. Several metabolic regulators exist as substrate responsive proteins chromosomally encoded as components of larger regulatory networks. For example, NtrC is part of the NtrBC two-component system that is not only involved in nitrogen assimilation, but also activation of a bacterial virulence program known as the stringent stress response. Activation of the stringent stress response alters the transcriptome of bacteria at a global level via expression of genes involved in biofilm formation and antibiotic resistance. Whole genome analyses have revealed that NtrC contributes to the success of P. aeruginosa in acute and chronic wound infections. Here, we propose to examine the influence of NtrC as well as other metabolically important regulators on virulence-associated rapid surface motilities. Active motility allows migration toward preferred nutrient sources away from stressors, colonization of host tissue and formation of surface-associated biofilms. Consistent with these roles, motility is intrinsically associated with bacterial metabolism and often coupled with the expression of virulence factors.