Alan J. Wolfe Ph.D.
Professor

Microbial Molecular Geneticist

Signal transduction and gene expression

We recently determined that a small phosphorylated molecule, acetyl phosphate (acP), influences the ability of E. coli cells to form biofilms, communities of bacteria that impact our health, our environment, and our industries. Using a DNA array analysis designed specifically to identify acP-responsive genes, we found that many acP-responsive genes function in the initial steps of biofilm formation. We then tested whether cells altered in their ability to produce or degrade acP could construct normal biofilms, and found that they could not. Now, we are dissecting the mechanisms by which acP coordinates the expression of its target genes, which encode structures, e.g., flagella, type 1 pili, and capsule, required to initiate biofilm development.

We also study how nucleoid-associated proteins (NAPs) regulate transcription of acs, a gene that helps E. coli cells survive starvation. It appears that NAPs, which function like eukaryotic histones to remodel chromatin, determine whether the transcription machinery gains access. Perhaps more intriguingly, these NAPs also seem to influence the contacts made between the machinery’s parts, e.g., RNA polymerase and specific transcription factors. These interactions appear to modulate the level of transcription. 

Selected Publications  

Sule, P., Wadhawan, T., Wolfe, A. J. and Prüß, B. M. 2008. Use of the BacTiter-Glo^TM microbial cell viability assasy to study bacterial attachment. Promega Notes. In press.

Wolfe, A. J., Parikh, N., Lima, B. P., and Zemaitaitis, B. 2008. Signal integration by the two-component signal transduction response regulator CpxR. J. Bacteriol. 190:2314-22.

Wolfe, A. J. and Visick, K. L. 2008. Get the message out:cyclic-di-GMP regulates multiple levels of flagellar-based motility. J. Bacteriol. 190:463-475.

Keating, D. H., A. Shulla, A. H. Klein, and A. J. Wolfe. 2008. Optimized two-dimensional thin layer chromatography to monitor the intracellular concentration of acetyl phosphateand other small phosphorylated molecules. Biological Procedures On-line I10:36-46.

Wolfe, A. J., and K. L. Visick. 2008. Get the message out: cyclic-di-GMP regulates multiple levels of flagellum-based motility. J. Bacteriol. I190:463-475.

Schwan, W.R., Shibata ,S., Aizawa, S.I., Wolfe, A.J.. The Two-Component Response Regulator RcsB Regulates Type 1 Piliation in Escherichia coli. J Bacteriol. 2007 Jul 20; Epub 2007 Jul 20. 

Sclavi, B., Beatty, C.M., Thach, D.S., Fredericks, C. E., Buckle, M, Wolfe, A. J. The multiple roles of CRP at the complex acs promoter depend on activation region 2 and IHF. Mol Microbiol. 2007 Jul;65(2):425-40. 

Klein, A.H., Shulla, A., Reimann, S.A., Keating, D. H., Wolfe, A. J. The Intracellular Concentration of Acetyl Phosphate in Escherichia coli Is Sufficient for Direct Phosphorylation of Two-Component Response Regulators. J Bacteriol. 2007 Aug;189(15):5574-81. Epub 2007 Jun 1. 

Visick, K. L,., O'Shea, T. M., Klein, A. H., Geszvain, K., Wolfe, A. J. The sugar phosphotransferase system of Vibrio fischeri inhibits both motility and bioluminescence. J Bacteriol. 2007 Mar;189(6):2571-4. Epub 2007 Jan 12. 

Fredericks, C. E., Shibata, S., Aizawa, S.-I., and Wolfe, A. J. (2006). Epistatic interactions between the Pta-AckA pathway and the Rcs phosphorelay regulate flagella biogenesis and capsule biosynthesis. Mol. Microbiol. 61:734-747.

 Prüß, B. M., Besemann, C., Denton, A., Wolfe, A. J. (2006). A transcription network controls the early stages of biofilm development in Escherichia coli. J Bacteriol 188:3731-3739.

Wolfe, A. J. (2005). The acetate switch. Microbiol Mol Biol Rev 69:12-50.

Browning, D. F., Lee, D. J., Wolfe, A. J., Cole, J. A., and Busby, S. J. W. The Escherichia coli K-12 NarL and NarP proteins insulate the nrf promoter from the effects of IHF. J Bacteriol. In Press.

Browning, D. F., Grainger, D. C., Beatty, C. M., Wolfe, A. J., Cole, J. A. and Busby, S. J. W. (2005). Integration of three signals at the Escherichia coli nrf promoter: a role for Fis protein in catabolite repression. Mol. Microbiol. 52:496-510.

O’Shea, T. M., Klein, A., Geszvain, K., Wolfe, A. J., and Visick, K. L. Diguanylate cyclases control magnesium-dependent motility of Vibrio fischeri. J Bacteriol. In Press.

O’Shea, T. M., DeLoney-Marino, C. R., Shibata, S., Aizawa, S.-I., Wolfe, A. J., and Visick, K. L. (2005). Magnesium promotes flagellation of Vibrio fischeri. J. Bacteriol. 187(6):2058-65

Search PubMed for a complete listing of Alan Wolfe's publications

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