Research - Meisenheimer Lab

Meisenheimer research group, Summer 2017
Left to right: Carson Hasselbrink, Breanna Arellano, Kristen Meisenheimer, Ben Stone, and Austin Gandler (next to Einstein)

The Meisenheimer Lab focuses on the organic synthesis of intracellular signaling molecules that bacteria use to communicate between each other. This bacterial communication process is called quorum sensing. Currently, the Meisenheimer Lab is preparing derivatives of substituted indoles known to inhibit bacterial biofilm formation. (Figure 1)

Here is an excellent article on the process of quorom sensing.

 

Figure 1 - Indole-Based Biofilm Inhibitors

A biofilm is a highly hydrated polysaccharide matrix that bound bacteria secrete.  Because of enhanced resistance to disinfection treatments and antibiotics, bacterial biofilms can cause persistent infections to humans in hospital settings, and equipment failure and severe corrosion in industrial settings.

 

Figure 2 - Pseudomonas aeruginosa colonizing on lung tissue

Credit: Juergen Berger/Science Photo Library

The ultimate goal of the Meisenheimer lab is to covalently link the indole-derivatives (Figure 3) to a polymeric coating synthesized by Dr. Erik Sapper’s lab (Cal Poly, Chemistry).  This coating can then be applied to surfaces where biofilms commonly form to inhibit their production by the bacteria.

 

Figure 3 - Substituted Indoles

Publications

1. Robins, L.I., Meisenheimer, K.M., Fogle, E.J., Chaplan, C.A., Redman, R.L., Vacca, J.T., Tellier, M.R., Collins, B.R., Duong, D.H., Schulz, K, Marlier, J.F., “A Kinetic Isotope Effect and Isotope Exchange Study of the Non-enzymatic and the Equine Serum Butyrylcholinesterase-Catalyzed Thioester Hydrolysis,” J. Org. Chem., 2013, 78 (23), pp 12029–12039.
2. Meisenheimer, K.M., Meisenheimer, P.L., Koch, T.H., "Nucleoprotein Photo-Crosslinking Using Halopyrimidine Substituted RNAs," Methods in Enzymology. 2000, 318, 88-104.
3. Meisenheimer, K. M.; Koch, T. H. "The Photocrosslinking of Nucleic Acids to Proteins," CRC Critical Reviews in Biochemistry and Molecular Biology 1997, 32(2), 101-140.
4. Norris, C. L.; Meisenheimer, K. M.; Koch, T. H. "Mechanistic Studies Relevant to Bromouridine Enhanced Nucleoprotein Photocrosslinking. Possible Involvement of an Excited Tyrosine Residue of the Protein," Photochem. Photobiol. 1997, 65(2), 201.
5. Meisenheimer, K. M.; Meisenheimer, P. L.; Willis, M. C.; Koch, T. H. "High Yield Photocrosslinking of a 5-Iodocytidine (IC) Substituted RNA to its Associated Protein," Nucl. Acids Res., 1996, 24(, 981.
6. Willis, M. C.; LeCuyer, K. A.; Meisenheimer, K. M.; Uhlenbeck, O. C.; Koch, T. H. "An RNA-Protein Contact Determined by 5-Bromouridine Substitution, Photocrosslinking, and Sequencing," Nucl. Acids Res. 1994, 22, 4947.