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Title: GENOMIC ANALYSIS OF MACROPHAGES INFECTED WITH M. TUBERCULOSIS, M. AVIUM AND M. SMEGMATIS.

Author
item McGarvey, Jeffery - Jeff
item Stanker, Larry
item Ravva, Subbarao
item BERMUDEZ, LUIZ - OREGON STATE UNIV.

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 2/5/2003
Publication Date: 2/10/2003
Citation: Mcgarvey, J.A., Stanker, L.H., Ravva, S.V., Bermudez, L. 2003. Genomic analysis of macrophages infected with m. tuberculosis, m. avium and m. smegmatis [Abstract]. Poster 5613.

Interpretive Summary: The mycobacteria are a group of bacteria that contain both disease causing and non-disease causing species. The disease causing mycobacteria infect a group of human cells called macrophages, a type of immune cell that usually kills invading bacteria. In order to determine how disease causing mycobacteria are able to infect these cells and survive while non-disease causing mycobacteria are killed by these cells we examined the gene expression patterns of macrophages infected with both types of mycobacteria. We found several differences in gene expression by macrophages infected with these different mycobacteria that may account for the different outcomes of the mycobacteria.

Technical Abstract: The mycobacteria are an insidious group of bacterial pathogens that cause the deaths of more people world-wide than any other group of organisms. One of the reasons these pathogens are so successful is that they are able to invade and replicate within host macrophages, one of the first lines of defense against intruding pathogens. In contrast, nonpathogenic mycobacteria, such as M. smegmatis are rapidly killed by macrophages. In order to better understand the series of events that allow pathogenic mycobacteria to survive and replicate within host macrophages, while the nonpathogenic mycobacteria are rapidly killed, we infected the human monocytic cell line U937 with pathogenic (M. tuberculosis and M. avium) and nonpathogenic (M. smegmatis) mycobacteria and monitored the expression of over 3,500 genes at 4, 12 and 24 h post inoculation using a commercially available gene array system. We observed multiple differences between the gene expression patterns of macrophages infected with pathogenic and nonpathogenic mycobacteria including genes involved in cytokine, lymphokine and chemokine production, adhesion, apoptosis, signal transduction, transcription, protein cleavage, actin polymerization and growth. From these data, we conclude that macrophages infected with pathogenic mycobacteria have altered gene expression patterns and that this altered gene expression is an important factor for the survival and multiplication of the pathogenic mycobacteria.