The well-publicized surge in antibiotic resistance, in the face of a dwindling drug pipeline heavily reliant on chemical modification of existing scaffolds, calls for the urgent development of novel, outside-the-box approaches to deal with the rising pathogen threats outlined by the Centers for Disease Control and Prevention in their 2013 Threat Report. In particular, therapeutic interventions designed to exploit natural or induced physiological vulnerabilities, while avoiding mechanisms used by drug resistant strains to evade antibiotic cytotoxicity, are of significant interest and would have transformative clinical potential.
Synthetic and Systems Biology are well-poised to aid in these pursuits, presenting a valuable framework for quantitatively addressing the imperative needs to: (1) better comprehend pathogen stress biology, (2) reduce antibiotic resistance and its development, and (3) aid in the diversification of our antibiotic armamentarium. In order to create effective new therapies or improve current treatment strategies, the dynamic metabolic and biochemical processes that affect antibiotic efficacy upon binding of drug to target must be better understood.
The meaningful questions I am motivated to address with these approaches are related to elucidating mechanistic details of the cell death process induced by lethal stress in bacterial pathogens underlying infectious disease.