Host-Microbe Program

Dr. McCormick is one of the original pioneers in the field now known as cellular microbiology. Her work provided the first evidence that epithelial cells in response to pathogen contact orchestrate a pro-inflammatory program, which recruits inflammatory cells. Dr. McCormick has since identified new, previously unidentified and unexpected virulence mechanisms that are key to the inflammatory response, leading to both novel biological principles of host-microbe interactions and therapeutic intervention strategies for infectious/non-infectious intestinal disorders.  In the course of this work Dr. McCormick challenged the dogma of bacterial type III secretion systems by prompting reconsideration of the long-held view that S. typhimurium effector proteins must be delivered into host cells by a type III secretion and translocation system. Dr. McCormick’s studies further led to the novel observation that Salmonella type III secreted effector proteins require processing by the host enzyme caspase-3 in order to be fully virulent. Bioinformatic analysis also showed this finding may generalize to other intestinal pathogens such as Shigella flexneri, enteropathogenic E. coli, and rotavirus.

Selected Publications:

1. Lee CA, Silva M, Siber AM, Kelly AJ, Galyov E, McCormick BA. A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12283-8.
   
   
2. Wall DM, Nadeau WJ, Pazos MA, Shi HN, Galyov EE, McCormick BA. Identification of the Salmonella enterica serotype typhimurium SipA domain responsible for inducing neutrophil recruitment across the intestinal epithelium. Cell Microbiol. 2007 Sep;9(9):2299-313.
   
   
3. Fukazawa, A., Alonso, C., Kurachi, K., Gupta, S., Lesser, C., McCormick, B.A., Reinecker, H.S. GEF- H1 dependent NF-kB activation in the recognition of Shigella effectors by NOD1. Plos Pathog. 2008 Nov;4(11):e1000228.
   
   
4. Srikanth CV, Wall DM, Maldonado-Contreras A, Shi HN, Zhou D, Demma Z, Mumy KL, McCormick BA. Salmonella pathogenesis and processing of secreted effectors by caspase-3. Science. 2010 Oct 15;330(6002):390-3.
   
   
5. Hallstrom KN, Srikanth CV, Agbor TA, Dumont CM, Peters KN, Paraoan L, Casanova JE, Boll EJ, McCormick BA. PERP, a host tetraspanning membrane protein is required for Salmonella-induced inflammation. Cell Microbiol. 2015 Jun;17(6):843-59.
   
   
6. Maldonado-Contreras A, Birtley JR, Boll E, Zhao Y, Mumy KL, Toscano J, Ayehunie S, Reinecker HC, Stern LJ, McCormick BA. Shigella depends on SepA to destabilize intestinal epithelial integrity via cofilin activation. Gut Microbes. 2017 Nov 2;8(6):544-560. 
   
   
7. Boll, E.J., Ayala-Lujan, J., Szabady, RL., Louissaint, C, Smith, RZ., Krogfelt, KA., Nataro, JP., Ruiz-Perez, F., McCormick, BA. Enteroaggregative Escherichia coli adherence fimbriae drive inflammatory cell recruitment via interactions with epithelia MUC1. MBio. 2017 Jun 6;8(3).