Molecular microbiology and microbial physiology and genetics. Regulation of gene expression in prokaryotes in response to environmental stress with special emphasis on acid stress responses; microbial pathogenesis.
Our lab is focused on prokaryotic research. A primary theme is the response of bacterial cells to environmental stress. In particular, several projects are concentrated on acid stress. This is important for both basic and applied research. There appears to be a correlation between the infectious dose of a bacterial pathogen and its ability to survive the acidity of the stomach. Moreover, since many foods are preserved with organic and inorganic acids, it is of concern that microbes, when exposed to foods, could obtain resistance to acidity. We are studying these processes at the molecular level. This includes identifying physiological conditions that confer protection to the bacterial cells, as well as the proteins and genes involved in these protective processes. Mutants resistant to acid have been isolated and are being characterized.
A second line of research studies transcription factors that influence acid sensitivity/resistance in Escherichia coli. One such protein is the integration host factor (IHF), which is a DNA binding and bending protein. We are presently studying the influence of this protein as a positive regulatory factor on the expression of three acid-inducible genes; the inducible arginine decarboxylase, the inducible lysine decarboxylase, and the inducible lysyl-tRNA synthetase. As a spin off of this work we are examining compounds that would target IHF binding sites as possible therapeutic agents.
Third, we are examining at the proteomic level, the interaction between a pathogenic bacterium, enteroinvasive Escherichia coli, and mammalian host cells. Initially two questions are of interest: what bacterial proteins are induced upon the invasion of the mammalian host, and what host proteins respond to the invading bacteria?
A. Paratore and I.N. Hirshfield. 2012. DNA Microarray Analysis of the Escherichia coli Small Colony Variant IH9 Reveals Differential Expression of Several Gene Groups.
V. Santos and I.N. Hirshfield. 2012. Phenotypic Rescue of an Escherichia coli Small Colony Variant by Lipoic Acid.
K. Dutta, A.W. Paratore, and I.N. Hirshfield. 2011. The Escherichia coli Small Colony Variant IH( has a Propensity for Biofilm Formation.
P. Basu and I.N. Hirshfield. 2011. Role of Heat Shock in Survival of Escherichia coli and its Small Colony Variant IH3 against Acid Stress. Int. J. Appl. Science Technol. 1:21-31.
Cohen, A., and I.N. Hirshfield. 1997. Effect of oxygen-reducing membrane fraction on Helicobacter pylori. J. Rapid Meth. Automat. Microbiol. 5: 299-307.
Ekholm, D. F. and I.N. Hirshfield. 2001. Rapid methods to enumerate Escherichia coli using 4-methyumbelliferyl-13-glucuronide. J. AOAC Int. 84:407- 415.
Paul, B.D. and LN. Hirshfield.1999. The response of log-phase Escherichia coli to varying levels of acid. Abstr. K-42, p137. Abstr. 99th Gen, Meet. Am. Soc. Microbiol.
Paul, B. D. and I.N. Hirshfield. 2001. Comparative analysis of the protein profile of enteroinvasive Escherichia coli strain 10012 cultured in acidic medium and in eukaryotic cells. Abstr. 1-24, p421. Abst. 101st Gen. Meet. Am. Soc.
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