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Microbial Pathogenesis

Research in my laboratory is directed at unraveling the complex regulatory circuits controlling changes in gene expression that occur when a bacterial cell encounters a hostile or nutrient-depleted environment. The model system we are currently using is the entry of Bacillus subtilis into a stationary growth phase at which time the cell must decide whether or not to embark along the developmental path leading to the formation of a dormant spore.  A number of genes that first become expressed at this time are regulated by a group of global regulatory proteins termed “transition state regulators”.  We are concentrating our present efforts on biochemical, structural and molecular genetic studies of the three most pleiotropic of these DNA-binding global regulators of transcription: the AbrB, Abh and ScoC proteins. We are conducting studies, including microarray transcriptome analyses, examining the effects of these regulators on the expression of a number of different operons which encode functions necessary for cellular adaptation to a variety of stressful conditions, the production of novel antibiotics, the initiation of biofilm formation and growth, survival and production of toxins in various environments. We also are continuing our investigations exploring how these regulators themselves are regulated by genetic and environmental factors.

We have discovered that AbrB possesses a novel DNA-binding motif (now termed the AbrB- fold) that allows it to flexibly interact with high affinity to a large number of different base sequences that presumably approximate an ideal 3-dimensional conformation. AbrB orthologs and paralogs have been discovered in all Bacillus, Clostridium, and  Listeria species examined.  As part of our studies we are investigating the DNA-binding properties of AbrB paralogs (Abh, SpoVT) in B. subtilis, and the AbrB orthologs found in other species. We hope that the information gained from our studies may one day allow us to design proteins, based on the AbrB-fold, that are capable of recognizing any particular subset of DNA sequences that we choose to target.

Dr. Strauch is director of the MICP511 Microbiology course for Dental Students

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