(a) Iron and oxidative stress
Within the cell, the labile iron pool is believed to not bound to proteins as cofactors but chelated in the ferrous form by metabolites. This iron may be oxidized by ferritin and stored as a ferric-oxide within the ferritin nanocage. Iron movement from the labile pool to ferritin is hypothesized to be in response to oxidative stress. Our aim is to show the conditions under which ferroxidation by ferritin is important for cell survival.
(b) Helical cell shape of epsilon-proteobacteria
The pathogens Campylobacter jejuni and Helicobacter pylori have helical cell shape used to burrow into mucosal layers of gastrointestinal track. Bacterial cell shape is defined by the structure of the peptidoglycan layer and helical bacteria have enzymes that modify this layer and are required for helical morphology. We are investigating the structure and function of these cell shape determining enzymes. This project is a collaboration with Dr. Tanner (Chemistry), Dr. Gaynor (Microbiology and Immunology) and Dr. Salma (FHCRC, Seattle).
(c) Antibiotic resistance by Burkholderia
Burkholderia cenocepacia complex is a group of bacteria that infect the lungs of cystic fibrosis patients. These bacteria are notoriously resistant to clinically available antibiotics. We are investigating two mechanisms responsible to broad antibiotic resistance by these bacteria. The first is the secretion of bacterial lipocalins which potentially bind antibiotics and the second is modification of lipid A (a collaboration with Dr. Valvano at Queen's University Belfast).
(d) Staphylococcal response to iron limitation
The bacterial pathogen Staphylococcus aureus uses iron for metabolism and to counter oxidative stress. During invasive infection, iron is acquired by S. aureus from host sources including heme from hemoglobin. Also, the pathogen adapts to iron limiting growth conditions by repressing iron-requiring pathways such as the TCA cycle and oxidative phosphorylation. We are investigating siderophore and heme-iron based uptake systems used by S. aureus to acquire iron from the human host environment. For example, IsdB is expressed on the bacterial cell surface and binds hemoglobin and extracts heme for use by S. aureus. Staphyloferrin B is a siderophore produced by S. aureus by the enzymes expressed from the sbn locus. We interested in understanding how staphyloferrin B is produced when S. aureus metabolism is operating under iron limitation. We are collaborating with Dr. Heinrichs (U. Western Ontario)
