Our lab is currently focused on these areas:
Cystic fibrosis research
People with cystic fibrosis develop lethal bacterial lung infections; studying these infections is a major focus of our lab. We use DNA-based (“microbiome”) analysis to better understand the causes of infection, genomics to study bacterial adaptations during infection, and proteomics to identify bacterial responses to lung conditions and treatments. We are also trying to better understand the growth of pathogens at chronic infection sites.
Studies of bacterial evolution during chronic human infections
Our lab identified mechanisms of bacterial diversification in biofilms, which are matrix-encased bacterial aggregates. We are now studying genetic diversification of bacteria during chronic human infections. Our data indicate that P. aeruginosa strains infecting cystic fibrosis (CF) patients extensively diversify during infection, in large part due to the isolation of bacteria in different lung regions. We are currently investigating the effects of pathogen diversification on disease manifestations and on the development of drug resistance in CF and wound infections.
A novel antibiotic that disrupts bacterial iron metabolism
A key natural mechanism of host defense is the withholding of iron from pathogens. We are studying the metal gallium as a “Trojan horse” to disrupt bacterial iron metabolism. Because of its similarity to iron, gallium is imported by many bacteria. However, gallium cannot undergo the sequential reduction and oxidation critical for iron’s biologic functions. Based on positive phase 1 study results, we are now performing a phase 2 clinical trial, and we are studying the antimicrobial and anti-inflammatory mechanisms of gallium.
Mechanisms of antibiotic tolerance
Antibiotic tolerance is decreased susceptibility of bacteria caused by phenotypic mechanisms, rather than due to the acquisition of resistance genes or gene mutations. Bacteria become antibiotic tolerant when aggregated, nutrient-deprived, or subjected to stress. Recent work from our lab showed that bacterial starvation triggers tolerance. We are now investigating how in vivo conditions may produce tolerance during infection.