Laboratory of Human Bacterial Pathogenesis

Program Description

Although most bacteria are killed readily by neutrophils, pathogens such as Staphylococcus 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 infectious pathogens such as community-associated (or -acquired) methicillin-resistant S. aureus (CA-MRSA). 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 specific emphasis on the interaction of bacterial pathogens with human neutrophils
• Investigates mechanisms mediating evasion of innate immunity by pathogens of special interest such as Staphylococcus aureus
• Identifies new virulence genes involved in the pathogenesis of infections caused by pathogens of special interest
• Uses appropriate ex vivo assays, animal models (including knock-out mice), and (if possible) human specimens to test hypotheses developed from in vitro analyses

Biography

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 disease in the department of medicine at the University of Iowa (1996 – 2000). Dr. DeLeo joined the staff at NIAID’s Rocky Mountain Laboratories in 2000. He currently serves on the editorial boards of Infection and Immunity, Apoptosis, and PLoS Pathogens.

Research Group

Scott D. Kobayashi, Ph.D. (Staff Scientist)
Natalia Malachowa, Ph.D. (Postdoctoral Fellow)
Kevin M. Rigby, Ph.D. (Postdoctoral Fellow)
Kevin R. Braughton (Microbiologist)
Adeline R. Whitney (Microbiologist)

Selected Publications

Kobayashi SD, DeLeo FR. A MRSA-terious enemy among us: boosting MRSA vaccines. Nat Med. 2011 Feb;17(2):168-9.

Kennedy AD, Porcella SF, Martens C, Whitney AR, Braughton KR, Chen L, Craig CT, Tenover FC, Kreiswirth BN, Musser JM, DeLeo FR. Complete nucleotide sequence analysis of plasmids in strains of Staphylococcus aureus clone USA300 reveals a high level of identity among isolates with closely related core genome sequences. J Clin Microbiol. 2010 Dec;48(12):4504-11.

Kennedy AD, Wardenburg JB, Gardner DJ, Long D, Whitney AR, Braughton KR, Schneewind O, DeLeo FR. Targeting of alpha-hemolysin by active or passive immunization decreases severity of USA300 skin infections in a mouse model. J Infect Dis. 2010 Oct 1;202(7):1050-8.

Ventura CL, Malachowa N, Hammer CH, Nardone GA, Robinson MA, Kobayashi SD, DeLeo FR. Identification of a novel Staphylococcus aureus two-component leukotoxin using cell surface proteomics. PLoS One. 2010 Jul 16;5(7):e11634.

Kobayashi SD, Braughton KR, Palazzolo-Ballance AM, Kennedy AD, Sampaio E, Kristosturyan E, Whitney AR, Sturdevant DE, Dorward DW, Holland SM, Kreiswirth BN, Musser JM, DeLeo FR. Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus. J Innate Immun. 2010 Jun 2(6):560-75.

Deleo FR, Otto M, Kreiswirth BN, Chambers HF. Community-associated meticillin-resistant Staphylococcus aureus.  Lancet. 2010 May 1;375(9725):1557-68.

Visit PubMed for a complete publication list.

Selected Data in Public Repositories

Microarray data for Voyich et al., 2005. J Immunol. 175: 3907-3919, are posted on the Gene Expression Omnibus as data series GSE2728.

Microarray data for Kobayashi et al., 2004. J Immunol. 172: 636-643, are posted on the Gene Expression Omnibus as data series GSE935.