In this mentored clinical scientist training proposal, the applicant will test the hypothesis that expression of global regulatory elements and virulence factors differs among various pulsotypes of methicillin-resistant Staphylococcus aureus (MRSA) and that increased expression of key genes will correlate with virulence in an established rat model of necrotizing pneumonia. In addition, gene expression will be evaluated using an in vivo assay and compared to expression seen in vitro. S. aureus isolates causing community-associated (CA-MRSA) disease will be compared with isolates causing health-care-associated (HA-MRSA) disease. These studies will provide an excellent opportunity for training in molecular biology, bacteriology, and utilization of animal models of disease. The applicant, Christopher P. Montgomery, MD, is an Instructor in the Section of Pediatric Critical Care at the University of Chicago. He formally entered the laboratory of Robert S. Daum, MD, in February 2006, with effort interdigitated with ongoing clinical responsibilities. Dr. Montgomery is in the process of acquiring additional basic science training and has developed a rat model of CA-MRSA necrotizing pneumonia and severe sepsis. The proposed training plan provides 80% protected time, exceptional opportunities to acquire new skills and experience in cellular and molecular biology, as well as didactic training in laboratory techniques and ethical research conduct. The plan also provides interactions with a number of experienced investigators across disciplines, facilitating Dr. Montgomery's transition into successful independent investigation and competitiveness for independent R01 support. CA-MRSA is an important human pathogen causing a variety of severe clinical syndromes, including necrotizing pneumonia and severe sepsis in previously healthy children. Emphasis will be placed on evaluating the differences between the S. aureus genetic background USA300, the dominant circulating CA- MRSA strain in the U.S., and USA400, which it replaced. Insight into the virulence mechanisms of USA300 will shed light on its success in the community.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Investigator Award (CIA) (K08)
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Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Huntley, Clayton C
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University of Chicago
Schools of Medicine
United States
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Zhao, Fan; Chong, Anita S; Montgomery, Christopher P (2016) Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection. Pathogens 5:
Zhao, Fan; Cheng, Brian L; Boyle-Vavra, Susan et al. (2015) Proteomic Identification of saeRS-Dependent Targets Critical for Protective Humoral Immunity against Staphylococcus aureus Skin Infection. Infect Immun 83:3712-21
Montgomery, Christopher P; David, Michael Z; Daum, Robert S (2015) Host factors that contribute to recurrent staphylococcal skin infection. Curr Opin Infect Dis 28:253-8
Jones, Marcus B; Montgomery, Christopher P; Boyle-Vavra, Susan et al. (2014) Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains. BMC Genomics 15:1145
Boyle-Vavra, Susan; Yin, Shouhui; Jo, Dae Sun et al. (2013) VraT/YvqF is required for methicillin resistance and activation of the VraSR regulon in Staphylococcus aureus. Antimicrob Agents Chemother 57:83-95
Humikowski, Catherine A; Qureshi, Nadia; Montgomery, Christopher P et al. (2012) Six-week-old with fever and fussiness. Pediatr Infect Dis J 31:538, 544
Dawson, Emily C; Montgomery, Christopher P; Frim, David et al. (2012) Is repeat head computed tomography necessary in children admitted with mild head injury and normal neurological exam? Pediatr Neurosurg 48:221-4
Montgomery, Christopher P; Boyle-Vavra, Susan; Roux, Agn├Ęs et al. (2012) CodY deletion enhances in vivo virulence of community-associated methicillin-resistant Staphylococcus aureus clone USA300. Infect Immun 80:2382-9
Jo, Dae Sun; Montgomery, Christopher P; Yin, Shaohui et al. (2011) Improved oxacillin treatment outcomes in experimental skin and lung infection by a methicillin-resistant Staphylococcus aureus isolate with a vraSR operon deletion. Antimicrob Agents Chemother 55:2818-23
Montgomery, Christopher P; Boyle-Vavra, Susan; Daum, Robert S (2010) Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection. PLoS One 5:e15177