Chairman, Department of Veterinary Pathobiology
McKee Professor of Microbial Pathogenesis
• 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
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
Tadepalli, S., T. G. Nagaraja, G.C. Stewart, and S.K. Narayanan. 2008. Leukotoxin operon and differential expressions of the leukotoxin gene in bovine Fusobacterium necrophorum subspecies. Anaerobe 14:13-18. PMID: 17988899
Tadepalli, S., G. C. Stewart, T.G. Nagaraja, S. S. Jang, and S. K. Narayanan. 2008. Fusobacterium equinum possesses a leukotoxin gene and exhibits leukotoxin activity. Vet. Microbiol. 127:89-96.
Tadepalli, S., G. C. Stewart, T.G. Nagaraja, and S. K. Narayanan. 2008. Human Fusobacterium necrophorum strains have a leukotoxin gene and exhibit leukotoxin activity. J. Med. Microbiol. 57:225-231. PMID: 18201990
Hsieh, H.-Y., C. W. Tseng, and G. C. Stewart. 2008. Regulation of Rot Expression in Staphylococcus aureus. J. Bacteriol. 190:546-554. PMID: 17981965
Thompson, B. M. and G. C. Stewart. 2008. Targeting of the BclA and BclB proteins to the Bacillus anthracis spore surface. Mol. Microbiol. 70:421-434. PMID: 18761690
Shaw, L. N., C. Lindholm, T. Prajsnar, M. C. Brown, E. Golonka, G. C. Stewart, A. Trakowski, and J. Potempa. 2008. Identification and characterization of sS, a missing component of the stress and virulence responses of Staphylococcus aureus. PLoS One 3(12):e3844. PMID: 19050758
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
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
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
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
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
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
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
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.
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
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
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
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
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
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):437-57. doi: 10.1128/MMBR.00050-15. PMID: 26512126
Adkins, P.R.F., J.R. Middleton, M.J. Calcutt, G.C. Stewart, and L.K. Fox. 2016. Speciation 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. doi: 10.1128/JCM.02239-16. [Epub ahead of print]. PMID: 28330895
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. 2016. TLR sensing of bacterial spore-associated RNA triggers host immune responses with protective and detrimental effects. J. Exp. Med. doi: 10.1084/jem.20161141. [Epub ahead of print]. PMID: 28400473