The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

Research in the Wilson laboratory involves studying the molecular interactions and biochemical mechanisms by which protein toxins produced by pathogenic bacteria cause their toxic effects on animal cells. When the bacterial toxins are released into the media of the host, they can interact with or even enter host cells and interfere with normal signal transduction and physiological function, thereby disrupting the delicate balance of cellular metabolism, often lethally. One project involves studying the structure, function and pathogenic mechanisms of the potent dermonecrotic toxins produced by Pasteurella multocida, Bordetella sp., E. coli, and Yersinia. Like many other toxins, these toxins are currently being used as potent tools for studying signal transduction pathways and physiological processes within cells. The laboratory is interested in understanding the underlying mechanism of how these toxins carry out their effects on these processes. For example, the laboratory has discovered that the pleiotropic effects on different tissue cells caused by the toxin from P. multocida is due to the diverse roles that the toxin’s targets have in different cell types, which in turn influence the cellular and organismic outcomes of toxin action.

Of particular interest to the laboratory is development of post-exposure anti-toxin therapeutics. This requires a global understanding of the downstream metabolic and signaling pathways that are affected by toxins, so as to identify potential sites for intervention. We have initiated proteomic and metabolomic research projects to identify biomarkers of cellular toxicity (i.e. toxicogenomics), which will be part of our new IGB Theme on Mining Microbial Genomics for Novel Antibiotics. As part of an inter-institutional collaborative effort (the NIH-sponsored Great Lakes Regional Center for Excellence in Biodefense and Emerging Infectious Diseases) to combat botulism, we are developing novel post-exposure anti-toxin therapeutics against botulinum neurotoxins as well as highly sensitive, high-throughput detection assays for distinguishing among botulinum neurotoxins. There is currently no effective antidote for preventing or reversing botulism or paralysis once exposure has occurred and symptoms of disease have initiated. A major goal of this translational biomedical research is to design novel anti-toxins for neuronal cell-specific delivery of post-exposure therapeutics.

As part of our new IGB Theme on Host-Microbe Systems, we have just begun research to exploit comparative and functional genomic technologies to study the dynamic interactions between the host and its commensal as well as pathogenic microbes, i.e. microbial ecology in the host environment. This research will initially focus on the complex ecosystem of the vaginal and gut microbiota and their impact on health and disease in human and nonhuman primates. A central goal is to elucidate pathogenic mechanisms of vaginal infections such as bacterial vaginosis and the role of normal and abnormal microbiota in disease susceptibility and progression. Studying both human and nonhuman primate vaginal ecosystems has the potential to address human biomedical questions by establishing an evolutionary and comparative biology context that considers environments, microbes, and host immune systems.

Representative Publications

Ho M; Goh C-H; Brothers MC; Wang S; Young RL; Ou Y; Lui JN-M; Kalafatis M; Lan X; Wolf AE; Rienstra CM; Wilson BA "Glycine insertion at protease cleavage site of SNAP25 resists cleavage but enhances affinity for botulinum neurotoxin serotype A" Protein Science (2011), in press

Wilson BA; Ho M (refereed review) “Cellular and molecular action of the mitogenic protein-deamidating toxin from Pasteurella multocida” FEBS Journal (2011), 278(23):4616-4632

White BA; Creedon DJ; Nelson KE; Wilson BA (refereed review) “The vaginal microbiome in health and disease” Trends Endocrin. Metab. (2011), 22(10):389-393

Brothers MC; Ho M; Maharjan R; Clemons NC; Bannai Y; Waites MA; Faulkner MJ; Kuhlenschmidt TB; Kuhlenschmidt MS; Blanke SR; Rienstra CM; Wilson BA “Membrane interaction of Pasteurella multocida toxin involves sphingomyelin” FEBS J (2011), 278(232):4633-4648

Wilson BA; Salyers AA; Whitt DD; Winkler ME. Bacterial Pathogenesis: A Molecular Approach (Third Edition), ASM Press, Washington, DC (2011) (textbook)

Repella T; Ho M; Chong TPM; Bannai Y; Wilson BA “The role of Arf6 protein in Pasteurella multocida toxin entry and trafficking” Toxins (2011) 3:218-241

Yeoman CJ; Chia N; Yildirim S; Berg Miller ME, Stumpf R, Leigh SR; Nelson KE; White BA; Wilson BA “Towards an Evolutionary Model of Animal-Associated Microbiomes” Entropy (2011) 13:570-594 (e13030570)

Ho M; Chang L-H; Pires-Alves M; Thyagarajan B; Bloom JE; Gu Z; Aberle KK; Bannai Y; Johnson SC; McArdle JJ; Wilson BA “Expression and purification of botulinum neurotoxin A heavy chain-based GFP-fusion proteins as prototype delivery vehicles for neuronal cell targeting” Protein Engineering, Design, and Selection (2011) 24(3):247-253

Wilson BA; Ho M “Recent insights into Pasteurella multocida toxin and other G-protein-modulating bacterial toxins” Future Microbiology (2010) 5(8):1185-1201

Yildirim S; Yeoman CJ; Sipos M; Torralba M; Wilson BA; Goldberg TL; Stumpf RM; Leigh SR; White BA; Nelson KE “Characterization of fecal microbiome from non-human wild primates reveals species specific microbial communities” PLoS ONE (2010) 5(11):e13963

Yeoman CJ; Yildirim S; Thomas SM; Durkin AS; Torralba M; Sutton G; Buhay CJ; Ding Y; Dugan-Rocha SP; Muzny DM; Qin X; Gibbs RA; Leigh SR; Stumpf R; White BA; Highlander S; Nelson KE; Wilson BA “Comparative genomics of Gardnerella vaginalis strains reveals substantial differences in metabolic and virulence potential” PLoS ONE (2010), 5(8):e12411

Gupta VR; Wilson BA; Blanke SR “Sphingomyelin is important for the uptake and intracellular trafficking of Helicobacter pylori VacA” Cellular Microbiology (2010), 12(10):1517-1533

Rivera AJ; Frank JA; Stumpf RM; Salyers AA; Wilson BA; Olsen GJ; Leigh S “Differences between the normal vaginal bacterial community of baboons and that of humans” Am. J. Primatol. (2010) 71:1-8

Dong J; Thompson AA; Fan Y; Lou J; Conrad F; Ho M; Pires-Alves M; Wilson BA; Stevens RC; Marks JD “A single-domain llama antibody potently inhibits the enzymatic activity of botulinum neurotoxin by binding to the non-catalytic alpha-exosite binding region” J. Mol. Biol. (2010) 397:1106-1118

Rivera AJ; Stumpf RM; Wilson BA; Leigh S; Salyers AA “Baboon vaginal microbiota: an overlooked aspect of primate physiology” Am. J. Primatol (2010) 72:467-474

Orth JHC; Preuß I; Fester I; Schlosser A; Wilson BA; Aktories K “Molecular mode of action of Pasteurella multocida toxin: Activation of heterotrimeric G proteins by deamidation” Proc. Natl. Acad. Sci. USA (2009) 106:7179-7184.

Kim TK; Thomas SM; Ho M; Sharma S; Reich C; Frank J; Yeater KM; Biggs D; Nakamura N; Stumpf R; Leigh SR; Tapping RI; Blanke SR; Slauch JM; Gaskins HR; Weisbaum JS; Olsen GJ; Hoyer LL, Wilson BA “Heterogeneity of vaginal microbial communities within individuals” J. Clin. Microbiol. (2009) 47:1181-1189.

Pires-Alves M; Ho M; Aberle KK; Janda KD; Wilson BA “Tandem fluorescent proteins as FRET-based substrates for botulinum neurotoxin activity” Toxicon (2009) 53:392-399

Orth JHC; Fester I; Preuß I; Agnoletto L; Wilson BA; Aktories K “Activation of Gαi and subsequent uncoupling of receptor-Gαi signaling by Pasteurella multocida toxin” J. Biol. Chem. (2008) 283:23288-23294.

Ozgen N; Obreztchikova M; Guo J; Elouardighi H; Dorn GW 2nd; Wilson BA; Steinberg SF “Protein kinase D links Gq-coupled receptors to cAMP response element-binding protein (CREB)-Ser133 phosphorylation in the heart” J. Biol. Chem. (2008) 283:17009-17019

Frank JA; Reich CI; Sharma S; Weisbaum JS; Wilson BA; Olsen GJ “Critical evaluation of two commonly-used primers for amplification of bacterial 16S rRNA genes” Appl. Environ. Microbiol. (2008) 74:2461-2470.

Aminova LR; Luo S; Bannai Y; Ho M; Wilson BA “The C3 domain of Pasteurella multocida toxin is the minimal domain responsible for activation of calcium and mitogenic signaling” Protein Science (2008) 17:1-5.

Luo S; Ho M; Wilson BA “Application of intact cell-based NFAT-β-lactamase reporter assay to study Pasteurella multocida toxin-mediated activation of calcium signaling pathway” Toxicon (2008) 51:597-605

Wilson BA “Global Biosecurity in a Complex, Dynamic World” Complexity (2008) 14(1):71-88

Aminova LR; Wilson BA “Calcineurin-independent inhibition of 3T3-L1 Adipogenesis by Pasteurella multocida toxin: Suppression of Notch1, stabilization of β-catenin and Pref1” Cellular Microbiology (2007) 9:2485-2496.

Baldwin MR; Tepp WH; Pier CL; Bradshaw M; Ho M; Wilson BA; Fritz RB; Johnson EA; Barbieri JT “Characterization of the antibody response to the receptor binding domain of botulinum neurotoxin serotypes A and E” Infect. Immun. (2005) 73:6998-7005.

Sabri A; Wilson BA; Steinberg SF “Dual Actions of the Gαq Agonist Pasteurella multocida Toxin to Promote Cardiomyocyte Hypertrophy and Enhance Apoptosis Susceptibility,” Circ. Res. (2002) 90:850-857.

Wilson BA; Aminova LR; Ponferrada VG; Ho M “Differential Modulation and Subsequent Blockade of Mitogenic Signaling and Cell Cycle Progression by Pasteurella multocida Toxin,” Infect. Immun. (2000), 68:4531-4538

Seo B; Choy EW; Maudsley; Miller WE; Wilson BA; Luttrell LM “Pasteurella multocida Toxin Stimulates Mitogen-activated Protein Kinase via Gq/11-dependent Transactivation of the Epidermal Growth Factor Receptor," J. Biol. Chem. (2000) 275:2239-2245

Wilson BA; Zhu X; Ho M; Lu L "Pasteurella multocida Toxin Activates the Inositol Triphosphate Signalling Pathway in Xenopus Oocytes via Gq-Coupled Phospholipase C-β1," J. Biol. Chem. (1997) 272:1268-1275

Complete Publications List