Shabnam is a third-year Chemistry graduate student at University of Minnesota in Erin Carlson’s lab, where she studies the enzymes involved in the biosynthesis of bacterial cell wall, with a specific emphasis on transpeptidases and transglycosylases. Born and raised in Tehran, Iran, she obtained her Pharm.D. from Tehran University of Medical Sciences, while as part of her thesis, she worked on the design and synthesis of different antinociceptive and anticholinesterase compounds. She enjoys reading, pottery, dancing and learning Spanish outside of the lab. Shabnam is interested in a career in either biotech or pharmaceutical industry, and seeks at this conference to learn about various career choices.
Profiling of β-Lactam Selectivity for Penicillin-Binding Proteins in Bacillus subtilis
and Methicillin-Sensitive and -Resistant Staphylococcus aureus
Bacteria are surrounded by a cell wall, which protects them against osmolysis, invading organisms and host defenses. A major component of this structure is the peptidoglycan, which is composed of sugar-based polymer chains known as glycans that are cross-linked by short oligo peptide units. Penicillin-binding proteins (PBPs) are membrane-associated proteins that are involved in peptidoglycan synthesis and have received much attention as crucial antibacterial targets, inhibited by the beta-lactams such as penicillin, and for their role in antibiotic resistance. However, the specific roles of each PBP family member in a bacterium has been under hot debate for several decades. To address this challenge, we propose to generate activity-based probes that are selective for a single or subset of PBPs to visualize these proteins in live cells. My thesis work is aimed at evaluating the relationship between the structure and activity of different PBPs by the design, synthesis and implementation of selective chemical probes to explore the transglycosylase (TG; polymerization of the glycan strand) and transpeptidase (TP; cross-linking between glycan chains) actions of these proteins.
The Carlson Group recently reported specificity data of 20 beta-lactam antibiotics for the PBPs in the clinically-important organisms, Streptococcus pneumoniae and Escherichia coli. These data provide a starting point to determine if known beta-lactams could act as scaffolds for the generation of selective imaging probes for the transpeptidase activities these proteins. I am dramatically expanding this data set to include Bacillus subtilis and Staphylococcus aureus, as an important model and a pathogenic microorganism, respectively.