Alan J. Wolfe, Ph.D.

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. 


Wolfe, A. J. and Visick, K. L. eds. (2010). The second messenger cyclic di-GMP. ASM Press. Washington, D.C.

Reviews, book chapters, commentaries

Wolfe, A. J. (2010). Sighting the Alien Within: a New Look at Bdellovibrio. J. Bacteriol.192:6327-8. PMID: 20952572

Wolfe, A. J. (2010). Introduction to second messengers: Lessons from cyclic AMP In The second messenger cyclic di-GMP. Wolfe, A. J. and Visick, K. L. (eds) ASM Press. Washington, D.C. pp.3-7.

Wolfe, A. J. And Visick, K. L. (2010). Roles of diguanylate cyclases and phosphodiesterases in motility and biofilm formation in Vibrio fischeri. In The second messenger cyclic di-GMP. Wolfe, A. J. and Visick, K. L. (eds) ASM Press. Washington, D.C. pp.186-200.

Visick, K. L. and Wolfe, A. J. Cyclic di-GMP: using the past to peer into the future. In The second messenger cyclic di-GMP. Wolfe, A. J. and Visick, K. L. (eds) ASM Press. Washington, D.C. pp. 323-332.

Hu, L. I., Lima, B. P., and Wolfe, A. J. (2010). Bacterial protein acetylation: the dawning of a new age. Molecular Microbiology. 77:15–21. PMID: 20487279

Wolfe, A. J. (2010). Physiologically relevant small phosphodonors link metabolism to signal transduction. Current Opinion in Microbiology. 13:204-9.

Wolfe, A. J. (2009). Transcribing Metabolism Genes: Lessons from a Feral Promoter. In Metabolic Pathway Engineering Handbook. C. Smolke (ed) CRC Press.

Primary Research Articles  

Reimann, S. A. and Wolfe, A. J. (2010). Constitutive Expression of the Maltoporin LamB in the Absence of OmpR Damages the Cell Envelope Journal of Bacteriology 193: 842–853. PMID: 21131484

Xu, H., Caimano, M., Lin, T. He, M., Radolf, J. D., Norris, S. J., Gheradini, F., Wolfe, A. J., and Yang, X. F. (2010). Role of acetyl-phosphate in activation of the Rrp2-RpoN-RpoS pathway in Borrelia burgdorferi. PLoS Pathog 6(9): e1001104. doi:10.1371/journal.ppat.1001104 PMID: 20862323

Prüß, B. M.,  Verma, K., Kumar, S., Wu, J., Sule, P. Samanta, P., Horne, S. M., Christianson, D., Stafslien, S. J., Wolfe, A. J., and Denton, A. (2010). Environmental and genetic factors that contribute to Escherichia coli K-12 biofilm formation. Arch. Microbiol. 192(9):715-28. PMID: 20559621

Selected Publications  

Sule P, Wadhawan T, Carr NJ, Horne SM, Wolfe AJ, Prüss BM. (2009). A combination of assays reveals biomass differences in biofilms formed by Escherichia coli mutants. Lett Appl Microbiol. 49(3):299-304. Epub 2009 Jun 23.PMID: 19552773

Reimann, S. A. and Wolfe, A. J. (2009). A critical process controlled by MalT and OmpR is revealed through synthetic lethality. Journal of Bacteriology 191:5320-24. PMID: 19502392

Sule, P., Wadhawan, T., Wolfe, A. J. and Prüß, B. M. (2008). Use of the BacTiter-GloTM 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 flagellum-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.

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.

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