• Cholera was first described in the 1600s and is the most common disease caused by bacteria of the genus Vibrio.

• Vibrio cholerae, the causative agent of cholera, infects 3 to 5 million people each year resulting in more than 100,000 deaths.

• V. cholerae, as well as V. parahaemolyticus and V. vulnificus, colonize the intestines and causes death by dehydration.

• No vaccines have been approved for use in the U.S. and most vaccines only result in temporary immunity.
   

   

The LPS of Gram-negative Bacteria

• LPS is a major surface component of Gram-negative cell membranes

• Important for structural integrity of the bacteria

• LPS is an endotoxin, upon release inducing a strong host immune response

• Mutations in LPS biosynthesis are often lethal

• LPS phenotype changes alter biofilm formation

Exploring Liopolysaccharides to Understand Bacterial Pathogenesis

Selected Publications

• Taylor, E. A.; Rinaldo-Matthis, A.; Li, L.; Ganhem, M.; Hazleton, K. Z.; Cassera, M. B; Almo, S. C.; Schramm, V. L., “Anopheles gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure and Inhibition,” Biochemistry, 2007, 46, 12405-12415.
• Luo, M.; Singh, V.; Taylor, E. A.; Schramm, V. L., “Transition State Structures of Human, Bovine and
  Plasmodium falciparum Adenosine Deaminases,” Journal of the American Chemical Society, 2007, 129, 8008-8017.
• Taylor, E. A.; Clinch, K.; Kelly, P. M.; Li, L.; Evans, G. B.; Tyler, P. C.; Schramm, V. L., “Acyclic Ribooxacarbenium Ion Mimics as Transition State Analogues of Human and Malarial Purine Nucleoside Phosphorylases,” Journal of the American Chemical Society, 2007, 129, 6984-6985.
• Tyler, P. C.; Taylor, E. A., Froehlich, R. F. G.; Schramm, V. L., “Synthesis of 5'-Methylthio Coformycins:
  Specific Inhibitors for Malarial Adenosine Deaminase,” Journal of the American Chemical Society, 2007, 129, 6872-6879.
• Taylor Ringia, E. A.; Tyler, P. C.; Evans, G. B.; Furneaux, R. H.; Murkin, A. S.; Schramm, V. L., "Transition State Analogue Discrimination by Related Purine Nucleoside Phosphorylases," Journal of the American Chemical Society, 2006, 128, 7126-7127.
• Taylor Ringia, E. A., Schramm, V. L., "Transition States and Inhibitors of the Purine Nucleoside Phosphorylase Family," Current Topics in Medicinal Chemistry, 2005, 5, 1237-1258.
• Lewandowicz, A; Taylor Ringia, E. A.; Ting, L.-M.; Kim, K; Tyler, P. C.; Evans, G. B.; Zubkova, O. V.; Mee, S.; Painter, G. F.; Lenz, D. H.; Furneaux, R. H.; Schramm, V. L., "Energetic Mapping of Transition State Analogue Interactions with Human and Plasmodium falciparum Purine Nucleoside Phosphorylases," Journal of Biological Chemistry, 2005, 280, 30320-30328.
• Ting, L.-M.; Shi, W.; Lewandowicz, A.; Singh, V.; Mwakingwe, A.; Birck, M. R.; Taylor Ringia, E. A.; Bench, G.; Madrid, D. C.; Tyler, P. C.; Evans, G. B.; Furneaux, R. H.; Schramm, V. L.; Kim, K., "Targeting a Novel Plasmodium falciparum Purine Recycling Pathway with Specific Immucillins," Journal of Biological Chemistry, 2005, 9547 - 9554.
• Thoden, J. B.; Taylor Ringia, E. A.; Garrett, J. B.; Gerlt, J. A.; Holden, H. M.; Rayment, I., "Evolution of Enzymatic Activity in the Enolase Superfamily: Structural Studies of the Promiscuous o-Succinylbenzoate Synthase from Amycolatopsis," Biochemistry, 2004, 42, 5716-5727.
• Taylor Ringia, E. A.; Garrett, J. B.; Thoden, J. B.; Holden, H. M.; Rayment, I.; Gerlt, J. A., "Evolution of Enzymatic Activity in the Enolase Superfamily: Functional Studies of the Promiscous o-Succinylbenzoate Synthase from Amycolatopsis," Biochemistry, 2004, 43, 224-229.
• Klenchin, V.A.; Taylor Ringia, E. A., Gerlt, J. A.; Rayment, I., "Evolution of Enzymatic Activity in the Enolase Superfamily: Structural and Mutagenic Studies of the Mechanism of the Reaction Catalyzed by o-Succinylbenzoate Synthase from Escherichia coli," Biochemistry, 2003, 42, 14427-14433.
• Taylor, E. A.; Palmer, D. R. J.; Gerlt, J. A., "Lesser "Burden Borne" by o-Succinylbenzoate Synthase: An "Easy" Reaction Involving a Carboxylate Carbon Acid," Journal of the American Chemical Society, 2001, 123, 5824-5825.
• Thompson, T. B.; Garrett, J. B.; Taylor, E. A.; Meganathan, R.; Gerlt, J. A.; Rayment, I., "Evolution of Enzymatic Activity in the Enolase Superfamily: Structure of o-Succinylbenzoate Synthase from Escherichia coli in Complex with Mg²⁺ and o-Succinylbenzoate," Biochemistry, 2000, 39, 10662-10676.