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P2-205 Differential Gene Expression Profiles in Bacillus anthracis Sterne-infected Human Primary Cells of Pulmonary, Gastrointestinal, and Cutaneous Origin

Monday, July 27, 2015
Exhibit Hall (Oregon Convention Center)
Saeed Khan , U.S. Food and Drug Administration-NCTR , Jefferson , AR
Bernard Marasa , U.S. Food and Drug Administration-NCTR , Jefferson , AR
Kidon Sung , U.S. Food and Drug Administration-NCTR , Jefferson , AR
Tao Han , U.S. Food and Drug Administration-NCTR , Jefferson , AR
James Fuscoe , U.S. Food and Drug Administration-NCTR , Jefferson , AR
Mohamed Nawaz , U.S. Food and Drug Administration-NCTR , Jefferson , AR
Introduction: Bacillus anthracis is a Gram-positive spore forming bacteria that is classified as a bioterror agent.  It causes three types of anthrax infections in humans and many species of animals with mortality rates of > 90%, > 25%, and < 1% in pulmonary, gastrointestinal, and cutaneous anthrax, respectively. Infection could be acquired via contact with farm animals, contaminated food supply, or bioterrorist attack.  

Purpose: The purpose of this study was to identify biomarkers that could be utilized in diagnostic and medical counter-measures from the transcriptomic gene expression profiles of human primary cutaneous (NHEK), gastrointestinal (InMyoFibs), and pulmonary (SAEC) cell lines at 1, 3, 5 and 24 h after infection with the spores of an avirulent strain of B. anthracis.

Methods: Three independent RNA samples from spore-challenged and control groups and Agilent human 4x44k whole genome arrays were used for microarray analysis. The raw data were normalized using 75% scaling and Student t-test to compute the significant gene list (P < 0.05 and fold change > 1.5). Common and cell-specific genes and biomarkers were identified by using Ingenuity Pathway Analysis Software.

Results: An up-regulation of 1729, 4981, 1539 genes, a down-regulation of 2178, 5558, 698 genes along with 36, 489, and 52 cell-specific genes was observed in NHEK, InMyoFibs, and SAEC cells, respectively. Nine biomarker genes and 68 miRNAs were commonly and significantly affected among three cell lines. Some of the key biomarkers included ITGB1, SGK1, DAB2, and ARAP3; immunological mediators such as CCL3/5/7, IL1A, IL6/8, LIF, TLR2 and transcriptional regulators including c-FOS, c-JUN, and NFκB.

Significance: Identification of target genes involved in the germination of spores and progression of anthrax, and establishing methods to silence them would help in developing novel medical counter-measure targets and reducing infection rates due to handling/consuming infected foods or bioterrorism.

Back to: Poster Session 2 – Laboratory and Detection Methods; Meat, Poultry and Eggs; Dairy and Beverages; Food Law and Regulation; General Microbiology; Modeling and Risk Assessment
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