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Bacterial Oxygen Sensing

Oxygen (O2) is an important environmental signal that must be sensed by bacteria due to its key role in respiration for aerobic and facultative anaerobic bacteria, as well as its toxicity to obligate anaerobes. Furthermore, O2 levels vary significantly within the environment and the human host, serving as a signal for the bacteria to alter growth phenotypes and virulence. Therefore, my group is working to understand a family of putative O2 sensing heme proteins, termed globin coupled sensors (GCSs). The major goals of the project are to to elucidate signal transduction mechanisms within the GCS family and identify downstream pathways/proteins controlled by GCS signaling. GCS proteins are widely distributed throughout bacteria and contain a sensor globin domain linked to an output domain that can regulate diverse functions, such as aerotaxis and biofilm formation.

To date, our studies have characterized diguanylate cyclase-containing GCSs, including the proteins from Bordetella pertussis (BpeGReg), causative agent of whooping cough, and Pectobacterium carotovorum (PccGCS), a plant pathogen that causes rotting of numerous agriculturally relevant crops, as well as a GCS from Vibrio brasiliensis that is involved in stress sensing. These studies have improved our understanding of the enzymatic and conformational changes that accompany O2 binding, and the features of the heme pocket that transmit the O2 binding signal. In addition, we have recently discovered that O2-dependent GCS signaling in P. carotovorum controls motility, virulence factor production, and rotting of a plant host, linking GCS signaling to bacterial pathogenesis.


Papers related to the GCS project:

  • Hoque, N.J.; Weinert, E.E. (2023) Control of bacterial second messenger signaling and motility by heme-based direct oxygen-sensing proteins. Curr. Opin. Microbiol. 76, 102396. DOI: 10.1016/j.mib.2023.102396

  • Fekete, F.J.; Marotta, N.J.; Liu, X.; Weinert, E.E. (2023) An O2-Sensing Diguanylate Cyclase Broadly Affects the Aerobic Transcriptome in the Phytopathogen Pectobacterium carotovorum. Front. Microbiol. DOI: 10.3389/fmicb.2023.1134742

  • Hoque, N.J.; Helm, M.P.; Weinert, E.E. (2023) In Vitro Measurement of Gas-Dependent and Redox-Sensitive Diguanylate Cyclase Activity. Methods Mol. Biol. 2648, 75-86. DOI: 10.1007/978-1-0716-3080-8_6

  • Patterson, D. C.; Weinert, E.E. (2023) Spectrophotometric Method for the Quantification and Kinetic Evaluation of In Vitro c-di-GMP Hydrolysis in the Presence and Absence of Oxygen. Methods Mol. Biol. 2648, 87-98. DOI: 10.1007/978-1-0716-3080-8_7

  • Patterson, D.C.; Liu, Y.; Das, D.; Yennawar, N.H.; Armache, J.-P.; Kincaid, J.R.; Weinert, E.E. (2021) Heme Edge Residues Modulate Signal Transduction Within a Bifunctional Homo-Dimeric Sensor Protein. Biochemistry. 60, 3801-3812. DOI: 10.1021/acs.biochem.1c00581

  • Patterson, D.C.; Perez Ruiz, M.; Yoon, H.*; Walker, J.A.; Armache, J.-P.; Yennawar, N.H.; Weinert, E.E. (2021) Differential Ligand-Selective Control of Opposing Enzymatic Activities Within a Bifunctional c-di-GMP Enzyme. Proc. Natl. Acad. Sci. USA. 118, e2100657118. DOI: 10.1073/pnas.2100657118

  • Walker, J.A.; Wu, Y.*; Potter, J.R.; Weinert, E.E. (2020) pi-Helix Controls Activity of Oxygen-Sensing Diguanylate Cyclases. Biosci. Rep. 40, BSR20193602. DOI: 10.1042/BSR20193602​

  • Rivera, S.^; Young, P.G.*^; Hoffer, E.D.; Vansuch, G.E.; Metzler, C.L.*; Dunham, C.M.; Weinert, E.E. (2018) Structural Insights into Oxygen-Dependent Signal Transduction within Globin Coupled Sensors. Inorg. Chem. 57, 14386-14395. DOI: 10.1021/acs.inorgchem.8b02584

  • Burns, J.L.; Jariwala, P.B.; Rivera, S.; Fontaine, B.M.; Briggs, L.; Weinert, E.E. (2017) Oxygen-Dependent Globin Coupled Sensor Signaling Modulates Motility and Virulence of the Plant Pathogen Pectobacterium carotovorum. ACS Chem. Biol. 12, 2070-2077. DOI: DOI: 10.1021/acschembio.7b00380

  • Burns, J.L.; Rivera, S.; Deer, D.D.; Joynt, S.C.; Dvorak, D.; Weinert, E.E. (2016) Oxygen and c-di-GMP Binding Control Oligomerization State Equilibria of Diguanylate Cyclase-Containing Globin Coupled Sensors. Biochemistry. 55, 6642-6651. DOI: 10.1021/acs.biochem.6b00526

  • Rivera, S.; Burns, J.L.; Vansuch, G.E.; Chica, B.; Weinert, E.E. (2016) Globin Domain Interactions Control Heme Pocket Conformation and Oligomerization of Globin Coupled sensors. J. Inorg. Biochem. 164, 70-76. DOI: 10.1016/j.jinorgbio.2016.08.016

  • Jia, X.; Wang, J.-b.; Rivera, S.; Duong, D.; Weinert, E.E. (2016) An O2-sensing stressosome from a Gram-negative bacterium. Nature Commun. 7, 12381. DOI: 10.1038/ncomms12381

  • Burns, J.L., Deer, D.D., Weinert, E.E. (2014) Oligomeric State Affects Oxygen Dissociation and Diguanylate Cyclase Activity of Globin Coupled Sensors. Mol. BioSyst. 10, 2823-2826. DOI: 10.1039/c4mb00366g

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