This proposal details a comprehensive 5-year program for Dr. Paul J Planet's career development in basic research in Infectious Diseases. Dr. Planet has designed his mentored research program to provide both additional scientific training and skills that will allow him to succeed as an independent investigator and physician-scientist. Dr. Planet's scientific training objective is to add to his background in molecular microbiology and phylogenetics by gaining experience in the areas of host-pathogen immunology, epidemiology, and microbiome studies. His career objective is to successfully make the transition to being an independent investigator. Alice Prince M.D. will be Dr. Planet's primary mentor for scientific and career development. Dr. Prince is a leader in the fields of host-pathogen interactions, innate immunity, and infectious diseases. Dr. Planet has established an advisory committee that will guide his scientific progress and career development that is composed of microbiologists (Dr. Noah Fierer, Dr. Franklin Lowy, Dr. Barry Kreiswirth) with expertise in microbial ecology, immunology, epidemiology, genomics, animal models, and pathogenesis. He will also utilize the considerable resources for career development and scientific collaboration at Columbia University. Dr. Planet's project focuses on the remarkable ability of Staphylococcus aureus to colonize and persist on human skin and mucosal tissues. Colonization by S. aureus is critical for the spread of disease, and it is a major risk factor for infection. The central hypothesis is that Staphylococcus aureus improves its ability to colonize by triggering the host's innate immune response to preferentially eliminate other commensal bacterial competitors. In a mouse model, Dr. Planet recently found that the ability of S. aureus to manipulate the host's immune response is due, in part, to production of Protein A (SpA). He has also shown that the variable tandem repeat region (Xr) of SpA appears to be critical for this effect. Preliminary data suggests that SpA may act by increasing expression of antimicrobial peptides produced by the host epithelium.
The specific aims of the proposal are to: (1) Test the hypothesis that the Xr region of SpA affects colonization of resident flora in a mouse model, and delineate the specific ecological shifts that occur. (2) Determine the primary elements of the human innate immune response that are triggered by Xr leading to clearance of other flora.

Public Health Relevance

Staphylococcus aureus is a common and aggressive human pathogen that first colonizes patients prior to causing infection. Almost 30% of healthy people carry S. aureus on their skin and mucous membranes. This proposal will identify the mechanisms that enable S. aureus to so effectively outcompete other microorganisms on human tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI101005-03
Application #
8685117
Study Section
Microbiology and Infectious Diseases Research Committee (MID)
Program Officer
Huntley, Clayton C
Project Start
2012-07-15
Project End
2015-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10032
Planet, Paul J; Diaz, Lorena; Rios, Rafael et al. (2016) Global Spread of the Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Latin American Variant. J Infect Dis 214:1609-1610
Planet, Paul J; Parker, Dane; Cohen, Taylor S et al. (2016) Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to Staphylococcus aureus Superinfection. MBio 7:e01939-15
Panesso, Diana; Planet, Paul J; Diaz, Lorena et al. (2015) Methicillin-Susceptible, Vancomycin-Resistant Staphylococcus aureus, Brazil. Emerg Infect Dis 21:1844-8
Planet, Paul J; Diaz, Lorena; Kolokotronis, Sergios-Orestis et al. (2015) Parallel Epidemics of Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Infection in North and South America. J Infect Dis 212:1874-82
Parker, Dane; Narechania, Apurva; Sebra, Robert et al. (2014) Genome Sequence of Bacterial Interference Strain Staphylococcus aureus 502A. Genome Announc 2:
Parker, Dane; Planet, Paul J; Soong, Grace et al. (2014) Induction of type I interferon signaling determines the relative pathogenicity of Staphylococcus aureus strains. PLoS Pathog 10:e1003951
Rossi, Flávia; Diaz, Lorena; Wollam, Aye et al. (2014) Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med 370:1524-31
Benson, Meredith A; Ohneck, Elizabeth A; Ryan, Chanelle et al. (2014) Evolution of hypervirulence by a MRSA clone through acquisition of a transposable element. Mol Microbiol 93:664-81
Ahn, D S; Parker, D; Planet, P J et al. (2014) Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to MRSA pneumonia. Mucosal Immunol 7:1366-74
Planet, Paul J; Narechania, Apurva; Hymes, Saul R et al. (2013) Bordetella holmesii: initial genomic analysis of an emerging opportunist. Pathog Dis 67:132-5

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