Major Areas of Research
- Neutrophil biology and function
- Evasion of innate immunity by bacterial pathogens
- Host interactions with antibiotic-resistant bacteria
Phagocytosis of MRSA by a human neutrophil.
Bacterial infection and host response.
Although most bacteria are killed readily by neutrophils, pathogens such asStaphylococcus aureus have evolved mechanisms to circumvent destruction by these key innate immune cells and thereby cause human infections. A better understanding of the bacteria-neutrophil interface at the cell and molecular levels will provide information critical to our understanding, treatment, and control of disease caused by bacterial pathogens.
The long-term objective of our research is to promote development of enhanced diagnostics, better prophylactic agents, and new treatments for emerging bacterial pathogens such as community-associated methicillin-resistant S. aureus(CA-MRSA) and carbapenem-resistant Klebsiella pneumoniae. To achieve that objective, the Pathogen-Host Cell Biology Section does the following:
- Conducts a systematic molecular dissection of steps involved in the pathogen-host interaction, with emphasis on the interaction of bacterial pathogens with human neutrophils
- Investigates mechanisms mediating evasion of innate immunity by bacterial pathogens
- Identifies new virulence genes involved in the pathogenesis of infections caused by pathogens of special interest
- Uses animal infection models and (if possible) human specimens to test hypotheses developed from in vitro analyses
Dr. DeLeo received his Ph.D. in microbiology from Montana State University in 1996, studying the molecular basis of superoxide generation by human neutrophils. He did his postdoctoral training in the area of innate immunity and infectious diseases in the Department of Medicine at the University of Iowa (1996–2000). Dr. DeLeo joined the staff at the NIAID Rocky Mountain Laboratories in 2000 and served previously as Acting Chief of the Laboratory of Human Bacterial Pathogenesis (2007-2013). He was appointed to the NIH Senior Biomedical Research Service in 2011 and is Chief of the Laboratory of Bacteriology.
- Infection and Immunity
- Journal of Innate Immunity
Scott Kobayashi, Ph.D. (Associate Scientist)
Natalia Malachowa, Ph.D. (Staff Scientist)
Adeline Porter, B.A. (Microbiologist)
Brett Freedman, M.S. (Biologist)
John Carlson, Ph.D. (Microbiologist)
Will McGuinness, B.S. (Post-baccalaureate Fellow)
Nygaard TK, Kobayashi SD, Freedman B, Porter AR, Voyich JM, Otto M, Schneewind O, DeLeo FR. Interaction of staphylococci with human B cells. PLoS One. 2016 Oct 6;11(10):e0164410. doi: 10.1371/journal.pone.0164410.
Malachowa N, Kobayashi SD, Quinn MT, DeLeo FR. NET confusion. Front Immunol. 2016 Jun 28;7:259. doi: 10.3389/fimmu.2016.00259.
Malachowa N, Kobayashi SD, Porter AR, Braughton KR, Scott DP, Gardner DJ, Missiakas DM, Schneewind O, DeLeo FR. Contribution of Staphylococcus aureus coagulases and clumping factor A to abscess formation in a rabbit model of skin and soft tissue infection. PLoS One. 2016 Jun 23;11(6):e0158293. doi: 10.1371/journal.pone.0158293.
Kobayashi SD, Porter AR, Dorward DW, Brinkworth AJ, Chen L, Kreiswirth BN, DeLeo FR. Phagocytosis and killing of carbapenem-resistant ST258 Klebsiella pneumoniae by human neutrophils. J Infect Dis. 2016 May 15;213(10):1615-22. doi: 10.1093/infdis/jiw001.
Kobayashi SD, Malachowa N, DeLeo FR. Pathogenesis of Staphylococcus aureus abscesses. Am J Pathol. 2015 Jun;185(6):1518-27. doi: 10.1016/j.ajpath.2014.11.030.