Dr. Aaron Smith
University of Maryland, Baltimore County
Department of Chemistry and Biochemistry
Friday, November 21, 2025
12:00 Noon
Room 120 – Meyerhoff Chemistry Building
“The ABCs of Prokaryotic Ferrous Iron (Fe2+) Transport & Sensing”
The acquisition of iron is essential in establishing infection by most unicellular pathogens. Under acidic and/or anoxic conditions, found in numerous host niches, ferrous iron (Fe2+) is prevalent and may be leveraged by pathogenic bacteria to cause disease, if it can be both sensed in, and acquired from, the host’s environment. To sense the presence of extracellular Fe2+, many bacteria use a two-component signal transduction system (TCS) that also regulates biofilm and quorum sensing, known as BqsRS. Using biophysical methods, we have characterized the binding, selectivity, and the signal transduction mechanism of the membrane His kinase, BqsS, and we have unraveled the structure-function relationship of the coupled response regulator, BqsR. Importantly, using both in vitro and in vivo approaches, we show that this system is a global regulator of metabolism in the opportunistic and increasingly antibiotic-resistant Gram-negative bacterium Pseudomonas aeruginosa. Moreover, we demonstrate that the feo operon, encoding the most widely distributed bacterial ferrous iron (Fe2+) uptake system known as Feo, is one of the major regulatory targets of the BqsRS system. While the Feo system is inadequately understood at the atomic, molecular, and mechanistic levels, we have worked to close this knowledge gap by deciphering the structure-function relationship of the soluble and membrane components of this system. Using a suite of structural, biophysical, and biochemical approaches, over the years we have developed a comprehensive mechanistic model of Feo-mediated Fe2+ uptake. When taken together, our results provide a holistic picture of bacterial Fe2+ homeostasis, which could be targeted for therapeutic developments to attenuate antibiotic resistance.