Department of Veterinary Pathobiology

George Stewart
Professor Emeritus

    • BS, North Texas State University, Denton, TX
    • PhD, University of Texas Health Sciences Center, Dallas, TX
    • Post-doc, University of North Carolina, School of Medicine, Chapel Hill, NC

Building Address: 471e Bond Life Sciences Center
Email:
StewartGC@missouri.edu

Research Emphasis: Regulation of virulence gene expression (Staphylococcus aureus, Staphylococcus pseudintermedius, Fusobacterium necrophorum); expression of sporulation-specific proteins in Bacillus anthracis; development of novel spore display platforms for bioremediation and vaccine development.

Bacterial virulence gene expression: A major emphasis in my lab is to understand the molecular genetic mechanisms governing virulence gene expression in Staphylococcus aureus, the canine pathogen Staphylococcus pseudintermedius and coagulase-negative staphylococcal mastitis pathogens. Understanding of the networks that regulate expression of virulence factors may lead to novel therapeutic intervention strategies.

Fusobacterium necrophorum is an anaerobic bacterium responsible for calf diphtheria, foot rot in sheep and cattle, and rumenitis-liver abscess complex in feedlot cattle. It is increasingly recognized as a pathogen of humans, as well. The principal virulence factor of this bacterium is a large molecular weight leukotoxin. My laboratory is involved with the characterization of this protein, determination of its specific mode of action against bovine polymorphonuclear leukocytes, and regulation of its expression. Utilizing a genomics approach, virulence factors responsible for host-specificity of infections is being investigated.

Spore-specific proteins of Bacillus anthracis: Anthrax is zoonotic disease that has taken on added importance because of concerns over bioterrorism. This bacterium survives in soil because it can produce endospores. The spore is the infectious form of this zoonotic pathogen. The outermost layer of the spore, the exosporium, is important for the initial interactions with the infected host. My laboratory is involved in characterization proteins making up the exosporium layer as well as elucidating the exosporium biosynthetic pathway.

Development of a spore display system for bioremediation and vaccine development:  My laboratory has developed a genetic system for protein display on the surface of spore of members of the Bacillus cereus family of bacteria (B. anthracis, B. thuringiensis, and B. cereus). The proteins are incorporated onto the spore surface in large numbers, are surface exposed, and are more stable than when they are in soluble form. This system is being investigated for use in bioremediation and vaccine applications.

Teaching: VPB5558/8458 Veterinary Public Health, VPB5552/5553, Veterinary Bacteriology & Mycology

Selected Publications:

  1. Tadepalli, S., S. K. Narayanan, G. C. Stewart, M. M. Chengappa, and T. G. Nagaraja. 2009. Fusobacterium necrophorum: A ruminal bacterium that invades liver to cause abscesses in cattle. Anaerobe 15:36-43. PMID: 18595747
  2. Thompson, B. M., H. Y. Hsieh, K. A. Spreng, and G. C. Stewart. 2010. The co-dependency of BxpB/ExsFA and BclA for proper incorporation into the exosporium of Bacillus anthracis. Molec. Microbiol. 79:799-813. PMID: 21255119
  3. Thompson, B.M., J.M. Binkley, and G. C. Stewart. 2011. Current physical and SDS extraction methods do not efficiently remove exosporium proteins from Bacillus anthracis spores. J. Microbiol. Meth. 85:143-148. PMID 21338631
  4. Thompson, B.M., B.C. Hoelscher, A. Driks, and G.C. Stewart. 2011. Localization and assembly of the novel exosporium protein BetA of Bacillus anthracis. J. Bacteriol. 193:5098-5104. PMID: 21821770
  5. Thompson, B.M., B.C. Hoelscher, A. Driks, and G.C. Stewart. 2012. Assembly of the BclB glycoprotein into the exosporium and evidence for its role in the formation of the exosporium 'cap' structure in Bacillus anthracis. Mol. Microbiol. 86:1073-1084. PMID: 22989026
  6. Spreng, K.M., B. M. Thompson, and G.C. Stewart. 2013. A genetic approach for the identification of exosporium assembly determinants of Bacillus anthracis. J. Microbiol. Meth. 93(1):58-67. PMID: 23411372
  7. Schofield, D.A., I. J. Molineux, N. J. Sharp, K. A. Spreng, C. Westwater, and G. C. Stewart. 2013. Bacillus anthracis diagnostic detection and rapid antibiotic susceptibility determination using “bioluminescent” reporter phage. J. Microbiol. Meth. 95:156-161. PMID: 23994352
  8. Calcutt, M. J., M. F. Foecking, H.-Y. Hsieh, J. Perry, G. C. Stewart, and J. R. Middleton. 2013. Genome sequence analysis of Staphylococcus equorum bovine mastitis isolate UMC-CNS-924. Genome Announc. Oct 17;1(5). doi:pii: e00840-13. 10.1128/genomeA.00840-13. PMID: 24136848.
  9. Calcutt, M. J., M. F. Foecking, H.-Y. Hsieh, J. Perry, G. C. Stewart, and J. R. Middleton. 2013. Draft genome sequence of Staphylococcus simulans UMC-CNS-990, isolated from a case of chronic bovine mastitis. Genome Announc. 2013 Dec 12;1(6). pii: e01037-13. doi: 10.1128/genomeA.01037-13. PMID: 24336375
  10. Calcutt, M.J., M. F. Foecking, T. G. Nagaraja, and G. C. Stewart. 2014. Draft genome sequence of Fusobacterium necrophorum subsp. funduliforme bovine liver abscess isolate B35. Genome Announc.  May 1;2(2). pii: e00412-14. doi: 10.1128/genomeA.00412-14. PMID: 24786958
  11. Fry, P.R., M. J. Calcutt, M. F. Foecking, H.-Y. Hsieh, D. G. Suntrup, J. Perry, G. C. Stewart, and J. R. Middleton. 2014. Draft genome sequence of Staphylococcus chromogenes strain MU 970, isolated from a case of chronic bovine mastitis. Genome Announc. 2014 Aug 14;2(4). pii: e00835-14. doi: 10.1128/genomeA.00835-14. PMID: 25125652
  12. Calcutt, M.J., M.F. Foecking, P.R. Fry, H.-Y. Hsieh, J. Perry, G.C. Stewart, D.T. Scholl, S. Messier, and J.R. Middleton. 2014. Draft genome sequence of bovine mastitis isolate Staphylococcus agnetis CBMRN 20813338. Genome Announc. 2(5). pii: e00883-14. doi: 10.1128/genomeA.00883-14. PMID: 25189590
  13. Calcutt, M.J., M. F. Foecking, H. Y. Hsieh, P.R. Adkins, G. C. Stewart, and J. R. Middleton. 2015. Sequence analysis of Staphylococcus hyicus ATCC 11249T, an etiological agent of exudative epidermitis in swine, reveals a type VII secretion system locus and a novel 116-kilobase genomic island harboring toxin-encoding genes. Genome Announc. 3(1). pii: e01525-14. doi: 10.1128/genomeA.01525-14. PMID: 25700402
  14. Stewart, G. C. 2015. The exosporium layer of bacterial spores: a connection to the environment and the infected host. Microbiol. Mol. Biol. Rev. 79(4):437-457. doi: 10.1128/MMBR.00050-15. PMID: 26512126
  15. Adkins, P.R.F., J.R. Middleton,  M.J. Calcutt, G.C. Stewart, and L.K. Fox. 2016. Species identification and strain-typing of Staphylococcus agnetis and Staphylococcus hyicus isolated from bovine milk using a novel multiplex PCR and pulsed-field gel electrophoresis. J. Clin. Microbiol. 55(6):1778-1788. doi: 10.1128/JCM.02239-16. PMID: 28330895
  16. Choo, M.-K., Y. Sano, C. Kim, K. Yasuda, X.-D. Li, X. Lin, M. Stenzel-Poore, L. Alexopoulou, S. Ghosh, E. Latz, I. R. Rifkin, Z. J. Chen, G. C. Stewart, H. Chong, and J. M. Park. 2017. TLR sensing of bacterial spore-associated RNA triggers host immune responses with protective and detrimental effects. J. Exp. Med. 214(5):1297-1311. doi: 10.1084/jem.20161141. PMID: 28400473
  17. Adkins PRF, Dufour S, Spain JN, Calcutt MJ, Reilly TJ, Stewart GC, Middleton JR. 2018. Cross-sectional study to identify staphylococcal species isolated from teat and inguinal skin of different-aged dairy heifers. J Dairy Sci. 101(4):3213-3225. doi: 10.3168/jds.2017-13974. PMID: 29397170
  18. Adkins PRF, Dufour S, Spain JN, Calcutt MJ, Reilly TJ, Stewart GC, Middleton JR. 2018. Molecular characterization of non-aureus Staphylococcus spp. from heifer intramammary infections and body sites. J Dairy Sci. 101(6):5388-5403. doi: 10.3168/jds.2017-13910. PMID: 29525303
  19. Ho KV, Lei Z, Sumner LW, Coggeshall MV, Hsieh HY, Stewart GC, Lin CH. 2018. Identifying antibacterial compounds in black walnuts (Juglans nigra) using a metabolomics approach. Metabolites. 8(4). pii: E58. doi: 10.3390/metabo8040058. PMID: 30274312
  20. Boone TJ, Mallozzi M, Nelson A, Thompson B, Khemmani M, Lehmann D, Dunkle A, Hoeprich P, Rasley A, Stewart G, Driks A. 2018. Coordinated assembly of the Bacillus anthracis coat and exosporium during bacterial spore outer layer formation. MBio. 9(6). pii: e01166-18. doi: 10.1128/mBio.01166-18. PMID: 30401771


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