David S. Weiss, PhD

ARTDTP Research Discipline:

Antibiotic-resistant bacterial pathogens are an increasing cause of hospital-acquired infections (1.7 million per year), leading to ~100,000 deaths and an estimated total healthcare cost of $28-$35 billion. A. baumannii is a major cause of such infections and strains have recently emerged which are resistant even to the “last line of defense” (e.g., polymyxin antibiotics). Unfortunately, there is a dearth of new drugs to treat such infections and very few in the pipeline. Compounding the problem, almost nothing is known about the host immune response to A. baumannii infection, making the development of immune-based therapeutics and vaccines very difficult. The Weiss laboratory is interested in determining the molecular basis of how A. baumannii becomes resistant to last line antibiotics. To this end, they have recently identified two novel proteins that are essential for polymyxin resistance in A. baumannii, showing that their deletion from highly resistant strains re-sensitizes them to polymyxins. They are interested in identifying new drug targets such as these and generating novel drugs to combat currently untreatable strains, as well as developing immune-based therapeutics including vaccines. Finally, they have recently identified a role for a bacterial CRISPR/Cas system in endogenous gene regulation, in contrast to the canonical role of such systems in defense against foreign DNA. The group is now manipulating this system to artificially "program" it to target diverse mRNAs for therapeutic purposes. 

ARTDTP Faculty Collaborators:

Rafi Ahmed, PhD
Graeme L. Conn, PhD
Mary R. Galinski, PhD
Joanna B. Goldberg, PhD
Arash Grakoui, PhD
Daniel Kalman, PhD
Dennis C. Liotta, PhD
Philip N. Rather, PhD
Jyothi Rengarajan, PhD
William M. Shafer, PhD
David S. Stephens, PhD