Stress Response and Regulatory Networks

A key effort in the Food Safety Lab is to develop a better understanding of stress response systems and regulatory networks in bacterial pathogens and to translate this knowledge into improved control strategies for foodborne pathogens. Foodborne pathogens have to be able to adapt to diverse environmental and stress conditions during foodborne transmission, including food associated stresses (low pH, salt, low temperature) and host associated stresses (e.g., low pH in the stomach, oxidative stress). Our research not only provides a better understanding of the mechanisms used by bacteria to adapt to stressful and rapidly changing environments, but also provides knowledge that can be used to develop better prevention and therapeutic approaches, including better growth inhibitors and growth inhibitor combinations that can be used in foods. Current research focuses specifically on developing on improved understanding of regulatory networks and stress response systems in Listeria monocytogenes and to translating this knowledge into improved control strategies and therapeutics.

Relevant Key Publications:

  • Cohn, A.R., R.H. Orsi, L.M. Carroll, R. Chen, M. Wiedmann, and R.A. Cheng. 2021. Characterization of Basal Transcriptomes Identifies Potential Metabolic and Virulence-Associated Adaptations Among Diverse Nontyphoidal Salmonella enterica Serovars. Front. Microbiol. 12. doi:10.3389/fmicb.2021.730411.
  • Gaballa, A., S. Sunil, E. Doll, S.I. Murphy, T. Bechtel, V. Guariglia-Oropeza, and M. Wiedmann. 2021. Characterization of the roles of activated charcoal and Chelex in the induction of PrfA regulon expression in complex medium. PLoS One 16. doi:10.1371/journal.pone.0250989.
  • Orsi, R.H., S. Chaturongakul, H.F. Oliver, L. Ponnala, A. Gaballa, and M. Wiedmann. 2021. Alternative σ factors regulate overlapping as well as distinct stress response and metabolic functions in Listeria monocytogenes under stationary phase stress condition. Pathogens 10. doi:10.3390/pathogens10040411.
  • Cheng, R.A., and M. Wiedmann. 2021. Recent Advances in Our Understanding of the Diversity and Roles of Chaperone-Usher Fimbriae in Facilitating Salmonella Host and Tissue Tropism. Front. Cell. Infect. Microbiol. 10. doi:10.3389/fcimb.2020.628043.
  • Gaballa, A., R.A. Cheng, A.S. Harrand, A.R. Cohn, and M. Wiedmann. 2021. The Majority of Typhoid Toxin-Positive Salmonella Serovars Encode ArtB, an Alternate Binding Subunit. mSphere 6. doi:10.1128/msphere.01255-20.
  • Henderson, L.O., A. Gaballa, R.H. Orsi, K.J. Boor, M. Wiedmann, and V. Guariglia-Oropeza. 2020. Transcriptional profiling of the L. monocytogenes PrfA regulon identifies six novel putative PrfA-regulated genes. FEMS Microbiol. Lett. 367. doi:10.1093/femsle/fnaa193.
  • Liu, Y., R.H. Orsi, A. Gaballa, M. Wiedmann, K.J. Boor, and V. Guariglia-Oropeza. 2019. Systematic review of the Listeria monocytogenes σ regulon supports a role in stress response, virulence and metabolism. Future Microbiol. 14:801–828. doi:10.2217/fmb-2019-0072.
  • Cheng, R.A., and M. Wiedmann. 2019. The ADP-ribosylating toxins of Salmonella. Toxins (Basel). 11. doi:10.3390/toxins11070416.
  • Gaballa, A., V. Guariglia-Oropeza, M. Wiedmann, and K.J. Boor. 2019. Cross Talk between SigB and PrfA in Listeria monocytogenes Facilitates Transitions between Extra- and Intracellular Environments. Microbiol. Mol. Biol. Rev. 83. doi:10.1128/mmbr.00034-19.
  • Cheng, R.A., C.R. Eade, and M. Wiedmann. 2019. Embracing diversity: Differences in virulence mechanisms, disease severity, and host adaptations contribute to the success of nontyphoidal Salmonella as a foodborne pathogen. Front. Microbiol. 10. doi:10.3389/fmicb.2019.01368.
  • Guariglia-Oropeza, V., R.H. Orsi, C. Guldimann, M. Wiedmann, and K.J. Boor. 2018. The Listeria monocytogenes bile stimulon under acidic conditions is characterized by strain-specific patterns and the upregulation of motility, cell wall modification functions, and the PrfA regulon. Front. Microbiol. 9. doi:10.3389/fmicb.2018.00120.
  • Miller, R.A., M.I. Betteken, X. Guo, C. Altier, G.E. Duhamel, and M. Wiedmann. 2018. The typhoid toxin produced by the Nontyphoidal Salmonella enterica Serotype javiana is required for induction of a DNA damage response in Vitro and systemic spread in Vivo. MBio 9. doi:10.1128/mBio.00467-18.
  • Liu, Y., R.H. Orsi, K.J. Boor, M. Wiedmann, and V. Guariglia-Oropeza. 2017. Home alone: Elimination of all but one alternative sigma factor in Listeria monocytogenes allows prediction of new roles for σB. Front. Microbiol. 8. doi:10.3389/fmicb.2017.01910.
  • Guldimann, C., V. Guariglia-Oropeza, S. Harrand, D. Kent, K.J. Boor, and M. Wiedmann. 2017. Stochastic and differential activation of σB and PrfA in Listeria monocytogenes at the single cell level under different environmental stress conditions. Front. Microbiol. 8. doi:10.3389/fmicb.2017.00348.
  • Carroll, L.M., J. Kovac, R.A. Miller, and M. Wiedmann. 2017. Rapid, high-throughput identification of anthrax-causing and emetic Bacillus cereus group genome assemblies via BTyper, a computational tool for virulencebased classification of Bacillus cereus group isolates by using nucleotide sequencing data. Appl. Environ. Microbiol. 83. doi:10.1128/AEM.01096-17.
  • Miller, R.A., and M. Wiedmann. 2016. The cytolethal distending toxin produced by nontyphoidal Salmonella serotypes javiana, montevideo, oranienburg, and mississippi induces DNA damage in a manner similar to that of serotype Typhi. MBio 7. doi:10.1128/mBio.02109-16.
  • Liu, Y., R. H. Orsi; K. J. Boor, M. Wiedmann, and V. Guariglia-Oropeza. 2016. An advanced Bioinformatics Approach for Analyzing RNAseq Data Reveals Sigma H-dependent Regulation of Competence Genes in Listeria monocytogenes. BMC Genomics 17:115.
  • Orsi, R. H., T. M. Bergholz, M. Wiedmann and K. J Boor. 2015. The Listeria monocytogenes strain 10403S BioCyc database. Database (Oxford) Vol. 2015: Mar 28; 2015. pii: bav027. doi: 10.1093/database/bav027.
  • Tang, S. R. Orsi, H. den Bakker, M. Wiedmann, K. Boor, and T. Bergholz. 2015. Transcriptomic analysis of Listeria monocytogenes Adaptation to Growth on Vacuum-Packed Cold Smoked Salmon. Appl. Environ. Micro. 81:6812-6824.
  • Guldimann, C., K. J. Boor, M. Wiedmann, and V. Guariglia-Oropeza. 2015. Resilience in the face of uncertainty: sigma B fine-tunes gene expression to support homeostasis in Gram-positive bacteria. Appl. Environ. Micro (accepted 05/15/2016; AEM00714-16R1).
  • Denes, T. and M. Wiedmann. 2014. Environmental responses and phage susceptibility in foodborne pathogens: Implications for Improving Applications in Food Safety. Current Opinion in Biotechnology 26: 45–49.
  • Bergholz, T., S. Tang, M. Wiedmann, and K. J. Boor. 2013. Nisin resistance of Listeria monocytogenes is increased by exposure to salt Stress and is mediated via LiaR. Appl. Environ. Micro. 79:5682-5688.
  • Tang, S., M. J. Stasiewicz, M. Wiedmann, K. J. Boor, and T. M. Bergholz. 2013. Efficacy of different antimicrobials on inhibition of Listeria monocytogenes growth in laboratory medium and on cold-smoked salmon. Int. J. Food Microbiol. 165:265-275
  • Ringus, D. L., A. Gaballa, J. D. Helmann, M. Wiedmann, and K. J. Boor. 2013. Fluoro-phenyl-styrene-sulfonamide, a novel inhibitor of σB, activity, prevents the activation of σB, by environmental and energy stresses in Bacillus subtilis. Journal of Bacteriology: 195: 2509-2517.
  • Ivy, R., M. Wiedmann, and K. J. Boor. 2012. Listeria monocytogenes grown at 7°C shows Reduced Acid Survival and an Altered Transcriptional Response to Acid Shock Compared to L. monocytogenes grown at 37°C. Appl. Environ. Micro. 78:3824-3836.
  • Bergholz, T., B. Bowen, M. Wiedmann, and K. Boor. 2012. Listeria monocytogenes shows temperature dependent and independent responses to salt stress, including responses that induce cross-protection to other stresses. Appl. Environ. Micro. 78: 2602-2612.
  • Palmer, M. E., S. Chaturongakul, M. Wiedmann, and K. J. Boor. 2011. The Listeria monocytogenes sB Regulon and its Virulence-Associated Functions are Inhibited by a Small Molecule. mBio 2(6). pii: e00241-11
  • Stasiewicz, M. J., M. Wiedmann, and T. M. Bergholz. 2011. The transcriptional response of Listeria monocytogenes during adaptation to lactate and diacetate includes synergistic changes that increase fermentative acetoin production. Appl. Environ. Microbiol. 77: 5294-5306.
  • Stasiewicz, M. J., M. Wiedmann, and T. M. Bergholz. 2011. The transcriptional response of Listeria monocytogenes during adaptation to lactate and diacetate includes synergistic changes that increase fermentative acetoin production. Appl. Environ. Microbiol. 77: 5294-5306
  • Nielsen, J.S., M. Halberg Larsen; E. M. Sternkopf Lillebæk, T. M. Bergholz; M. H. G. Christiansen, K. J. Boor, M. Wiedmann, and B. H. Kallipolitis. 2011. A small RNA controls expression of the chitinase ChiA in Listeria monocytogenes.  PLoS ONE 6:e19019
  • Chaturongakul, S., S. Raengpradub, M. E. Palmer, T. M. Bergholz, R. H. Orsi, Y. Hu, J. Ollinger, M. Wiedmann, and K. J. Boor. 2010. Transcriptomic and phenotypic analyses identify coregulated, overlapping regulons among PrfA, CtsR, HrcA and the alternative sigma factors σB, σC, σH, and σL in Listeria monocytogenes.  Appl. Environ. Micro. 77:187-200
  • Ivy, R. A., Chan, Y. C., Bowen, B. M., Boor, K. J., and Wiedmann, M. 2010. Growth temperature-dependent contributions of response regulators, sB, PrfA, and motility factors to Listeria monocytogenes invasion of Caco-2 cells. Foodborne Pathog Dis. 7: 1337-1349
  • Oliver, H. F., R. H. Orsi, L. Ponnala, U. Keich, W. Wang, Q. Sun, S. W. Cartinhour, M. J. Filiatrault, M. Wiedmann, and K. J. Boor. 2009. Deep RNA sequencing of L. monocytogenes reveals overlapping and extensive stationary phase and sigma B-dependent transcriptomes, including multiple highly transcribed noncoding RNAs. BMC Genomics 10(1):641
  • Oliver, H. F., R. H. Orsi, M. Wiedmann, and K. J. Boor. 2010. Listeria monocytogenes sB has a small core regulon and a conserved role in virulence, but differential contributions to stress tolerance, across a diverse collection of strains. Appl. Environ. Micro. 76:4216-4232.