Characterization of a novel three-component toxin-antitoxin module from the pathogenic bacterium Escherichia coli O157:H7

Activiteit: Talk or presentation at a conference


Background: The paaR2-paaA2-parE2 operon is a unique three-component toxin-antitoxin module present in pathogenic Escherichia coli O157:H7 and a possible target for the development of new antibacterial drugs (Hallez et al., 2010; Sterckx et al., 2016). Aside from the toxin (ParE2) and antitoxin (PaaA2), the operon encodes an additional regulator (PaaR2) that is involved in the regulation of the transcription of the operon. Objectives: The objective of this work is to understand how PaaR2 autoregulates the transcription of the operon and if this regulation is possibly linked to the onset of persistence. Methods: Via a combination of structural biology, biochemistry and biophysical experiments, a mechanistic model for the autoregulation of the paaR2-paaA2-parE2 operon is constructed. Results: PaaR2 and an adjacent repressor have been found to regulate transcription of the paaR2-paaA2-parE2 operon and of a neighboring operon in a mechanism that resembles the CI-Cro repression mechanism from bacteriophage λ. References: Hallez, R., Geeraerts, D., Sterckx, Y., Mine, N., Loris, R., & Van Melderen, L. (2010). New toxins homologous to ParE belonging to three-component toxin-antitoxin systems in Escherichia coli O157:H7. Molecular Microbiology, 76(3), 719–32. Sterckx, Y. G.-J., Jové, T., Shkumatov, A. V., Garcia-Pino, A., Geerts, L., De Kerpel, M., Lah, J., De Greve, H., Van Melderen, L., Loris, R. (2016). A unique hetero-hexadecameric architecture displayed by the E. coli O157 PaaA2-ParE2 antitoxin-toxin complex. Journal of Molecular Biology, 428(8):1589-603.
Periode7 jul 201911 jul 2019
EvenementstitelFEMS 8th Congress of European Microbiologists
LocatieGlasgow, United Kingdom
Mate van erkenningInternational