@article{milton_draughn_bobay_stowe_olson_feldmann_thompson_myers_santoro_kearns_et al._2020, title={The Solution Structures and Interaction of SinR and SinI: Elucidating the Mechanism of Action of the Master Regulator Switch for Biofilm Formation in Bacillus subtilis}, volume={432}, ISSN={["1089-8638"]}, DOI={10.1016/j.jmb.2019.08.019}, abstractNote={Bacteria have developed numerous protection strategies to ensure survival in harsh environments, with perhaps the most robust method being the formation of a protective biofilm. In biofilms, bacterial cells are embedded within a matrix that is composed of a complex mixture of polysaccharides, proteins, and DNA. The gram-positive bacterium Bacillus subtilis has become a model organism for studying regulatory networks directing biofilm formation. The phenotypic transition from a planktonic to biofilm state is regulated by the activity of the transcriptional repressor, SinR, and its inactivation by its primary antagonist, SinI. In this work, we present the first full-length structural model of tetrameric SinR using a hybrid approach combining high-resolution solution nuclear magnetic resonance (NMR), chemical cross-linking, mass spectrometry, and molecular docking. We also present the solution NMR structure of the antagonist SinI dimer and probe the mechanism behind the SinR-SinI interaction using a combination of biochemical and biophysical techniques. As a result of these findings, we propose that SinI utilizes a residue replacement mechanism to block SinR multimerization, resulting in diminished DNA binding and concomitant decreased repressor activity. Finally, we provide an evidence-based mechanism that confirms how disruption of the SinR tetramer by SinI regulates gene expression.}, number={2}, journal={JOURNAL OF MOLECULAR BIOLOGY}, author={Milton, Morgan E. and Draughn, G. Logan and Bobay, Benjamin G. and Stowe, Sean D. and Olson, Andrew L. and Feldmann, Erik A. and Thompson, Richele J. and Myers, Katherine H. and Santoro, Michael T. and Kearns, Daniel B. and et al.}, year={2020}, month={Jan}, pages={343–357} }
 @article{milton_allen_feldmann_bobay_jung_stephens_melander_theisen_zeng_thompson_et al._2017, title={Structure of the Francisella response regulator QseB receiver domain, and characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based compounds}, volume={106}, ISSN={["1365-2958"]}, DOI={10.1111/mmi.13759}, abstractNote={With antibiotic resistance increasing at alarming rates, targets for new antimicrobial therapies must be identified. A particularly promising target is the bacterial two-component system. Two-component systems allow bacteria to detect, evaluate and protect themselves against changes in the environment, such as exposure to antibiotics and also to trigger production of virulence factors. Drugs that target the response regulator portion of two-component systems represent a potent new approach so far unexploited. Here, we focus efforts on the highly virulent bacterium Francisella tularensis tularensis. Francisella contains only three response regulators, making it an ideal system to study. In this study, we initially present the structure of the N-terminal domain of QseB, the response regulator responsible for biofilm formation. Subsequently, using binding assays, computational docking and cellular studies, we show that QseB interacts with2-aminoimidazole based compounds that impede its function. This information will assist in tailoring compounds to act as adjuvants that will enhance the effect of antibiotics.}, number={2}, journal={MOLECULAR MICROBIOLOGY}, author={Milton, Morgan E. and Allen, C. Leigh and Feldmann, Erik A. and Bobay, Benjamin G. and Jung, David K. and Stephens, Matthew D. and Melander, Roberta J. and Theisen, Kelly E. and Zeng, Daina and Thompson, Richele J. and et al.}, year={2017}, month={Oct}, pages={223–235} }
 @article{feldmann_cavanagh_2015, title={Teaching old drugs new tricks: Addressing resistance in Francisella}, volume={6}, ISSN={["2150-5608"]}, DOI={10.1080/21505594.2015.1053689}, number={5}, journal={VIRULENCE}, author={Feldmann, Erik A. and Cavanagh, John}, year={2015}, month={Jul}, pages={414–416} }