Maryland Chemist 2015
~ Dr. Angela Wilks ~
Department of Pharmaceutical Science
University of Maryland, Baltimore
Turning Bloodsucking Bacteria Anemic:
An Innovative Antibacterial Strategy
Wednesday, December 10, 6:00 pm-9:00 p.m.
Knott Science Center
Note Dame of Maryland University
4701 N Charles St.
Baltimore, MD 21212
The ability of iron to readily shift between the ferrous (Fe(II)) and ferric (Fe(III)) oxidation states has provided Nature a mechanism to drive a wide range of essential life processes including, dioxygen transport, energy transducing pathways, and nitrogen and hydrogen fixation. However, despite its abundance and versatility in Nature bioavailability of iron is extremely low. The fine balance of maintaining adequate iron levels while preventing the deleterious effects of excess iron has led to the evolution of sophisticated cellular mechanisms to obtain, store and regulate iron across all life forms. Within the context of infectious disease pathogens must acquire iron from the host by stripping it from high affinity iron binding proteins such as transferrin and ferritin, or, alternatively from the acquisition and degradation of heme. The opportunistic pathogen P. aeruginosa in chronic infection adapts to utilize heme and ferrous iron as the primary source of iron at the expense of iron-siderophore systems.
Our research seeks to gain a fundamental structural and mechanistic understanding of heme coordination, transport and utilization by bacterial pathogens through a systems biology approach employing bacterial genetics, metabolomics, biochemical and biophysical approaches. Structural and mechanistic characterization of the P. aeruginosa heme uptake proteins and their contributions to heme and iron homeostasis will be presented. The release of iron by oxidative cleavage of heme to biliverdin by heme oxygenase (HemO) is required to drive the metabolic flux of heme into the cell and as such represents a novel therapeutic target for future antibacterial drug development. The concept of “metabolic competence” as an antimicrobial strategy will be presented along with preliminary data on “hit to lead” inhibitors of HemO as novel antibacterials.
6:00 – 6:45 pm
Registration / Networking
$20 for members/nonmembers, $10 for students
RSVP (by December 5th)
Directions to Notre Dame of Maryland University:
From the north:
- Take the Baltimore Beltway (I-695) to North Charles Street (exit 25).
- Drive 4.6 miles south on Charles Street
- The University entrance is on the left, immediately past Homeland Avenue but before Cold Spring Lane.
From the Inner Harbor
- Take I-83 north 4.4 miles to Cold Spring Lane East (exit 9A).
- Drive 1.3 miles on W. Cold Spring Lane
- Turn left onto North Charles Street. The University entrance is .4 miles on the right.