Department of Biological Sciences

School of Natural Sciences and Mathematics

Stephen Spiro, PhD

Stephen Spiro
Professor and
Head of Department
BSB 12.102E
972-883-6032
Lab Webpage

Education and Professional Affiliations

B.Sc., Molecular Biology, University of Edinburgh, UK.
Ph.D., Molecular Biology and Microbiology, University of Sheffield, UK.
Postdoctoral Fellow, University of Sheffield, UK.
Before joining UTD Dr. Spiro held Faculty positions at the University of East Anglia, UK, and the Georgia Institute of Technology.

Overview

Dr. Spiro’s research is currently focused on responses to nitric oxide, a toxic free radical that is a by-product of normal metabolic processes in bacteria, as well as being a chemical defense synthesized by host phagocytic cells in response to infection by pathogenic microorganisms.

Research Interests

Nitric oxide (NO) is a water-soluble free-radical gas that is toxic in biological systems by virtue of its reactivity towards proteins, metal ions, lipids and DNA. Eukaryotic phagocytic cells exploit this toxicity by synthesizing NO as one of the arsenal of poisonous molecules that are used to kill invading pathogens. Successful intra-cellular pathogens (such as Salmonella and Mycobacterium species) are able to resist phagocyte killing mechanisms. There is increasing evidence that the ability to detoxify NO is required by some pathogens for survival inside host cells.

NO is also synthesized by Bacteria as an intermediate or by-product of normal respiratory processes. Specifically, nitrite can be used as an electron acceptor for anaerobic respiration by the denitrifying Bacteria, which reduce nitrite to NO, and also use NO as an electron acceptor, reducing it to nitrous oxide. The enteric Bacteria reduce nitrite to ammonia, but also catalyze the reduction of nitrite to NO, such that NO is made at a low concentration as a by-product of nitrite respiration. Escherichia coli has three enzymes that reduce or oxidize NO to less toxic compounds, and we speculate that one or more of these enzymes has a role in protecting the cell against the NO that is made endogenously from nitrite. The same enzymes may allow pathogens such as Salmonella to detoxify the NO made by host cells.

All three NO detoxification systems are up-regulated by exposure to nitrite or NO, and we have discovered and characterized two distinct regulatory mechanisms involved, using E. coli as a model system.We have defined the mechanism of NO sensing by the transcription factor NorR and charaterized the cis-acting regulatory sequences required for activation of its target genes (which encode a flavorubredoxin that reduces NO to nitrous oxide). We discovered a transcriptional repressor, NsrR, that regulates expression of a flavohemoglobin, which oxidizes NO to nitrate. We have used high throughput methods to define NsrR binding sites across the entire E. coli genome and so to identify novel genes regulated by NsrR.

More recent work has focused on the denitrifying bacterium Paracoccus denitrificans, which reduces nitrate to dinitrogen under anaerobic growth conditions.  This pathway (called denitrification) is important for soil fertility, greenhouse gas emission, and in waste and water treatment processes.  We are currently characterizing a novel signal transduction pathway that is triggered by NO.  The immediate goal is to identify the processes that are regulated and the molecular mechanisms involved. 


A complete list of publications can be found in ResearcherID, Orcid, or Google Scholar.    

Selected Recent Publications:

  • Mehta, H.H., Liu, Y., Zhang, M.Q. and Spiro S. (2015) Genome-wide analysis of the response to nitric oxide in uropathogenic Escherichia coli CFT073.  Microbial Genomics 1: doi: 10.1099/mgen.0.000031
  • Chhabra, S. and Spiro, S. (2015) Inefficient translation of nsrR constrains the behaviour of the NsrR regulon in Escherichia coli. Microbiology 161: 2029-2038.
  • Zeng, J. and Spiro, S. (2013) Finely-tuned regulation of the aromatic amine degradation pathway in Escherichia coliJournal of Bacteriology 195: 5141-5150.
  • McKethan, B.L. and Spiro, S. (2013) Cooperative and allosterically controlled nucleotide binding regulates the DNA binding activity of NrdR.  Molecular Microbiology 90: 278-289.
  • Spiro, S. and D'Autréaux, B. (2012) Non-heme iron sensors of reactive oxygen and nitrogen species.  Antioxidants and Redox Signaling 17: 1264-1276.
  • Spiro, S. (2012) Nitrous oxide production and consumption: regulation of gene expression by gas-sensitive transcription factors.  Proceedings of the Royal Society B 367: 1213-1225.
  • Spiro, S. (2011) Another target for NO.  Cell Host and Microbe 10: 1-2.
  • Browning, D.F., Lee, D.J., Spiro, S. and Busby, S.J. (2010) Down-regulation of the Escherichia coli K-12 nrf promoter by binding of the NsrR nitric oxide-sensing transcription repressor to an upstream site.  Journal of Bacteriology 192: 3824-3828.
  • Wang, Y., Dunn, A.K., Wilneff, J., McFall-Ngai, M.J., Spiro, S. and Ruby, E.G. (2010) Vibrio fischeri flavohaemoglobin protects against nitric oxide during initiation of the squid-Vibrio symbiosis.  Molecular Microbiology 78: 903-915.
  • Spiro, S. and Dixon R., Editors. (2010) Sensory mechanisms in bacteria. Molecular aspects of signal recognition. Caister Academic Press, U.K. (Edited Book)
  • Spiro, S. (2010) An alternative route to nitric oxide resistance.  Molecular Microbiology 77: 6-10.
  • Partridge, J.D., Bodenmiller, D.M., Humphrys, M.S. and Spiro, S. (2009). NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility.  Molecular
  • Updated: July 28, 2017