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

Community MRSA (red) causes destruction of human neutrophils (neutrophil debris, yellow).
Credit: NIAID

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 NIAID’s Rocky Mountain Laboratories in 2000 and is currently a senior investigator in the Laboratory of Human Bacterial Pathogenesis (LHBP). He has served as acting chief of the LHBP since 2007 and was appointed to the NIH Senior Biomedical Research Service in 2011.

Editorial Boards

• Apoptosis
• Infection and Immunity
• PLoS Pathogens (Associate Editor)

Research Group

Scott D. Kobayashi, Ph.D. (Staff Scientist)
Natalia Malachowa, Ph.D. (Postdoctoral Fellow)
Thea Lu, Ph.D. (Postdoctoral Fellow)
Adeline R. Whitney, B.S. (Microbiologist)

Selected Publications

Malachowa N, Kobayashi SD, Braughton KR, Whitney AR, Parnell MJ, Gardner DJ, DeLeo FR. Staphylococcus aureus leukotoxin GH promotes inflammation. J Infect Dis. 2012 Oct;206(8):1185-93.

Graves SF, Kobayashi SD, Braughton KR, Whitney AR, Sturdevant DE, Rasmussen DL, Kirpotina LN, Quinn MT, DeLeo FR. Sublytic concentrations of Staphylococcus aureus Panton-Valentine leukocidin alter human PMN gene expression and enhance bactericidal capacity. J Leukoc Biol. 2012 Aug;92(2):361-74.

Uhlemann AC, Porcella SF, Trivedi S, Sullivan SB, Hafer C, Kennedy AD, Barbian KD, McCarthy AJ, Street C, Hirschberg DL, Lipkin WI, Lindsay JA, DeLeo FR, Lowy FD. Identification of a highly transmissible animal-independent Staphylococcus aureus ST398 clone with distinct genomic and cell adhesion properties. mBio. 2012 Feb 28;3(2).

DeLeo FR, Kennedy AD, Chen L, Bubeck Wardenburg J, Kobayashi SD, Mathema B, Braughton KR, Whitney AR, Villaruz AE, Martens CA, Porcella SF, McGavin MJ, Otto M, Musser JM, Kreiswirth BN. Molecular differentiation of historic phage-type 80/81 and contemporary epidemic Staphylococcus aureus. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):18091-6.

Kobayashi SD, Malachowa N, Whitney AR, Braughton KR, Gardner DJ, Long D, Bubeck Wardenburg J, Schneewind O, Otto M, DeLeo FR. Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection.
J Infect Dis. 2011 Sep 15;204(6):937-41.

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.