Abstract

Coxiella burnetii is an obligate intracellular pathogen of humans. Spore-like particles develop during bacterial infection that are highly infectious when aerosolized. Very little is known about virulence determinants produced by C. burnetii, however, a type IV secretion system associated with this pathogen is thought to deliver proteins into mammalian host cells that enable intracellular trafficking and replication of the organism. We have identified multiple C. burnetii proteins that are substrates of this type IV secretion system. In this project we will use SILAC-labeling techniques to identify mammalian proteins targeted by these C. burnetii type effectors. Biochemical, genetic and proteomic approaches will be used to determine the in vivo function of these virulence determinants.

Public Health Relevance

These studies will provide unique insight into the mechanism used by C. burnetii to establish infection in eukaryotic host cells, information that is essential for future development of vaccines and Pharmaceuticals that can combat infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057158-10
Application #
8444630
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
10
Fiscal Year
2013
Total Cost
$340,946
Indirect Cost
$25,570

  Institution

Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Li, Xiao-Ping; Kahn, Jennifer N; Tumer, Nilgun E (2018) Peptide Mimics of the Ribosomal P Stalk Inhibit the Activity of Ricin A Chain by Preventing Ribosome Binding. Toxins (Basel) 10:
Goldman, David L; Nieves, Edward; Nakouzi, Antonio et al. (2018) Serum-Mediated Cleavage of Bacillus anthracis Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase. mSphere 3:
Marié, Isabelle J; Chang, Hao-Ming; Levy, David E (2018) HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies. J Exp Med 215:3194-3212
Uhde, Melanie; Ajamian, Mary; Wormser, Gary P et al. (2017) Reply to Naktin. Clin Infect Dis 64:1145-1146
Chen, Han; Coseno, Molly; Ficarro, Scott B et al. (2017) A Small Covalent Allosteric Inhibitor of Human Cytomegalovirus DNA Polymerase Subunit Interactions. ACS Infect Dis 3:112-118
Aguilar, Jorge L; Varshney, Avanish K; Pechuan, Ximo et al. (2017) Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300 Staphylococcus aureus. Virulence 8:741-750
Zhou, Yijun; Li, Xiao-Ping; Chen, Brian Y et al. (2017) Ricin uses arginine 235 as an anchor residue to bind to P-proteins of the ribosomal stalk. Sci Rep 7:42912
Lauretti, Flavio; Chattopadhyay, Anasuya; de Oliveira França, Rafael Freitas et al. (2016) Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection. Hum Vaccin Immunother 12:2327-33
Tadin, Ante; Tokarz, Rafal; Markoti?, Alemka et al. (2016) Molecular Survey of Zoonotic Agents in Rodents and Other Small Mammals in Croatia. Am J Trop Med Hyg 94:466-73
Basu, Debaleena; Li, Xiao-Ping; Kahn, Jennifer N et al. (2016) The A1 Subunit of Shiga Toxin 2 Has Higher Affinity for Ribosomes and Higher Catalytic Activity than the A1 Subunit of Shiga Toxin 1. Infect Immun 84:149-61

Showing the most recent 10 out of 655 publications