Biological weapons, as well as naturally occurring emerging and reemerging infectious diseases, are among the greatest threats to the safety of the US population. This risk is accentuated by the fact that the category ABC priority pathogens are rarely encountered in the US in clinical settings, and as a result the level of preparedness to respond to such threats remains alarmingly low. Therefore, we are proposing to identify molecular biomarker signatures for category B pathogens by creating a consortium with investigators working in areas of the world where they are causing substantial morbidity and mortality. We will pursue an alternative and potentially complementary approach to direct pathogen detection by developing diagnostic markers based on the assessment of the host transcriptional response to infection. Indeed, we have already demonstrated that dramatic changes in blood gene expression profiles occur during the acute phase of an infection, and that those changes are pathogen-specific. In the context of this project: (1) we will collect blood samples from well characterized patients with sepsis (Burkholderia pseudomallei / Khon Kaen University, Thailand), persistent fever (Brucella sp. / Centre d'lmmunologie de Marseille Luminy, France) and diarrheal diseases (Escherichia coli, pathogenic Vibrio strains, Shigella spp, Salmonella, Campylobacter jejuni and Caliciviruses / Department of Molecular Biomedicine, CINVESTAV&Microbiology Research Laboratory at Hospital General O'Horan of Merida, Mexico);(2) we will identify candidate diagnostic signatures and indicators of disease severity for infectious diseases caused by category B priority pathogens using a genome-wide blood transcriptional screen (48,000 transcripts);and (3) we will validate candidate blood markers using a focused transcriptional assay. In summary, this program will support a productive network of investigators, including research clinicians, research scientists with expertise in the immunology and genomics fields, as well as an experience support team of bioinformaticians and biostatisticians who will work together towards the development of novel tools that will improve the management of patients with infections caused by category B priority pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI082110-04
Application #
8133447
Study Section
Special Emphasis Panel (ZAI1-MMT-M (J1))
Program Officer
Hall, Robert H
Project Start
2009-08-18
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$1,310,765
Indirect Cost
Name
Benaroya Research Institute at Virginia Mason
Department
Type
DUNS #
076647908
City
Seattle
State
WA
Country
United States
Zip Code
98101
Patzi-Vargas, Sandra; Zaidi, Mussaret Bano; Perez-Martinez, Iza et al. (2015) Diarrheagenic Escherichia coli carrying supplementary virulence genes are an important cause of moderate to severe diarrhoeal disease in Mexico. PLoS Negl Trop Dis 9:e0003510
Rinchai, Darawan; Riyapa, Donporn; Buddhisa, Surachat et al. (2015) Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils. Autophagy 11:748-55
Speake, Cate; Presnell, Scott; Domico, Kelly et al. (2015) An interactive web application for the dissemination of human systems immunology data. J Transl Med 13:196
Alsina, Laia; Israelsson, Elisabeth; Altman, Matthew C et al. (2014) A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4. Nat Immunol 15:1134-42
Khaenam, Prasong; Rinchai, Darawan; Altman, Matthew C et al. (2014) A transcriptomic reporter assay employing neutrophils to measure immunogenic activity of septic patients' plasma. J Transl Med 12:65
Zaidi, Mussaret Bano; Estrada-García, Teresa (2014) Shigella: A Highly Virulent and Elusive Pathogen. Curr Trop Med Rep 1:81-87
Estrada-Garcia, Teresa; Perez-Martinez, Iza; Bernal-Reynaga, Rodolfo et al. (2014) Enteroaggregative coli: A Pathogen Bridging the North and South. Curr Trop Med Rep 1:88-96
Chaussabel, Damien; Baldwin, Nicole (2014) Democratizing systems immunology with modular transcriptional repertoire analyses. Nat Rev Immunol 14:271-80
Zaidi, Mussaret B; Estrada-García, Teresa; Campos, Freddy D et al. (2013) Incidence, clinical presentation, and antimicrobial resistance trends in Salmonella and Shigella infections from children in Yucatan, Mexico. Front Microbiol 4:288
Obermoser, Gerlinde; Presnell, Scott; Domico, Kelly et al. (2013) Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines. Immunity 38:831-44

Showing the most recent 10 out of 19 publications