Our lab is using molecular microbiological, molecular genetics, biochemical, and proteomic based approaches to define how bacteria interact with and respond to changes in the environment. Our goal is to understand the signal transduction pathways bacteria use to (1) sense environmental conditions, and then (2) to alter the proteins displayed on their cell surface. Since these cell surface changes enhance survival, we will develop strategies to interrupt these adaptive pathways, thereby controlling bacterial growth or infection.
Please note that I am not accepting new graduate students for the 2016-2017 academic year.
Understanding how Salmonella typhimurium senses and adapts to changes in the environment
Understanding how these changes enhance bacterial survival
Using proteomics to understand how posttranslational events are used by bacteria to respond to changes in the environment
Details of Research Interests:
We initiated an effort to characterize the disulphide oxidoreductases of Salmonella enterica serovar Typhimurium and found two periplasmic "foldases" that act to assist protein folding and are especially important to cell function when bacteria are growing in stressful conditions. One is a homologue of DsbA from E.coli, an enzyme that has been crystallized and has undergone extensive biochemical analysis. The second enzyme, called SrgA, is a substrate specific disulphide oxidoreductase that functions to oxidize cysteine resides in the PEF pilin subunit. As this work progressed we became interested in the transcriptional regulation of these foldases and this led to our current work studying the regulation of stress response proteins in S. typhimurium via a two component histidine kinase signal transduction pathway.
Bacteria survive in a multitude of diverse niches within the host organism and the ability to adapt to the specific challenges presented by each of these niches is key to establishing infection. Bacteria utilize several histidine kinase signal transduction pathways to sense and respond to changes outside of the cell. The lab currently focuses on two central issues related to sensing and responding to environmental stresses mediated by the Cpx histidine kinase pathway in S. typhimurium. First, we are attempting to map the types of environmental signals that stimulate specific stress response pathways. Using a proteomic-based approach coupled with transcriptional analysis of specific Cpx-responders we are comparing the responses of wild type and various mutant strains to a variety of stressors. Second, we are using a combined proteomic and biochemical approach to identify downstream responses in the Cpx signal transduction pathway. For example, we believe that a serine/threonine kinase is responsible for propagating the Cpx-initiated signal along one branch of the Cpx pathway. Serine/threonine kinases are poorly understood in bacterial systems, however our work is leading to an appreciation of how posttranslational events such as phosphorylation play a central role in bacterial adaptation and survival in the host. These studies will greatly enhance our understanding of bacterial virulence mechanisms and show us, perhaps, new approaches to controlling organisms that cause infectious disease.
Martin, N.L., P. Bass, and Steven N. Liss. 2015. Antibacterial properties and mechanism of activity of a novel silver-stabilized hydrogen peroxide. PLoS One 10(7): e0131345
Spreadbury, I., F. Ochoa Cortes, C. Ibeakanma, N.L. Martin, D. Hurbut, and S. Vanner, 2015. Concurrent psychological stress and infectious colitis is key to sustaining enhanced peripheral sensory signaling. Neurogastroenterol Motil. 27(3):347-355
Richards, M., and N.L. Martin. Histidine-mediated signal transduction, phospho-relay pathways in bacteria, mitochondria and eukaryotic cells. (under revision)
Martin, N.L. Protein expression profiling of the envelope stress responsive two component signaling pathway in Salmonella typhimurium. (under revision)
Paul, C., E. Cheung, and N.L. Martin. Binding of interferon gamma and biofilm formation in Pseudomonas aeruginosa is affected by the structure of a disulfide-bonded domain in OprF (under revision)
Ibeakanma C, Miranda-Morales M, Richards* M, Bautista-Cruz F, Martin N, Hurlbut D, Vanner S. 2009. Citrobacter rodentium colitis evokes post-infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons. Journal of Physiology, 587(Pt 14):3505-21
Martin, N.L. 2007. Sequence plus structure plus experimental inquiry: combining the clues to elucidate bacterial kinase function. Future Microbiol. 2(3):223-226
Zheng, J., C. He, V. K. Singh, N. L. Martin, and Z. Jia. 2007. Crystal structure of a novel Ser/Thr kinase and its implication in the Cpx stress response. Molec. Microbiol. 63:1360-1371
Gallant, C.V., T. Ponnampalam, H. Spencer, J.C.D. Hinton, and N.L. Martin. 2004. Exponential growth phase regulation of dsbA expression is controlled by HNS levels in Salmonella typhimurium. J. Bacteriol. 186(4):910-918
Roberts, M.D., N.L. Martin, and A.M. Kropinski. 2004. The genome and proteome of coliphage T1. Virology 318:245-266
Suntharalingam, P. H. Spencer, C. Gallant, and N.L. Martin. 2003 Salmonella enterica serovar Typhimurium rdoA is growth phase regulated and involved in relaying Cpx-induced signals. J. Bacteriol. 185: 432-443
Bouwman, C., M. Kohli, A. Killoran, G. Touchie, R. Kadner, and N.L. Martin. 2003. Characterization of SrgA, a Salmonella enterica serovar Typhimurium virulence plasmid-encoded paralogue of the disulfide oxidoreductase DsbA, essential for biogenesis of plasmid-encoded fimbriae. J. Bacteriol. 185:991-1000
Goecke, M., C. Gallant, P. Suntharalingam, and N.L. Martin. 2002. Salmonella typhimurium dsbA is growth phase regulated. FEMS Lett. 206: 229-234
Turcot, I., Ponnampalam, T.V., Bouwman, C.V., Martin, N.L. 2001. Isolation and characterization of a chromosomally encoded disulphide oxidoreductase from Salmonella enterica serovar Typhimurium. Can. J. Microbiol. 47: 711-721