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1 Department of Microbiology and Immunology, University of Arizona, Tucson, AZ 85724, USA
2 Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea
3 School of Molecular Bioscience, Washington State University, Pullman, WA 99164, USA
4 Tuberculosis Research Section, National Institute of Allergy and Infectious Disease, Rockville, MD 20852, USA
Correspondence
Linoj P. Samuel
Linoj_Samuel{at}urmc.rochester.edu
The eis gene of Mycobacterium tuberculosis has been shown to play a role in the survival of the avirulent Mycobacterium smegmatis within the macrophage. In vitro and in vivo analysis of
eis deletion mutants and complemented strains showed no effect on survival of M. tuberculosis in U-937 macrophages or in a mouse aerosol infection model, respectively. Further studies were done in an attempt to determine the role of eis in M. tuberculosis intracellular survival and to define a phenotypic difference between wild-type and the
eis deletion mutant. Bioinformatic analysis indicated that Eis is an acetyltransferase of the GCN5-related family of N-acetyltransferases. Immunofluorescence microscopy and Western blot analysis studies demonstrated that Eis is released into the cytoplasm of M. tuberculosis-infected U-937 macrophages. Eis was also found in the extravesicular fraction and culture supernatant of M. tuberculosis-infected macrophages. The effect of Eis on human macrophage cytokine secretion was also examined. Eis modulated the secretion of IL-10 and TNF-
by primary human monocytes in response both to infection with M. tuberculosis and to stimulation with recombinant Eis protein. These results suggest that Eis is a mycobacterial effector that is released into the host cell to modulate inflammatory responses, possibly via transcriptional or post-translational means.
, tumour necrosis factor alpha
Present address: Department of Clinical Microbiology, The University of Rochester, 601 Elmwood Ave, Box 710, Rochester, NY 14642, USA.
Present address: Amgen Inc., Thousand Oaks, CA 91320, USA.
Present address: Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USA.
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