NDLI: Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth.

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Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth.

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Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Steyn, Adrie J. C. Hondalus, Mary K. Kawakami, R. Pamela Jacobs, William R. Collins, Desmond M. Bloom, Barry R.
Description	Author Affiliation: Steyn AJ ( Harvard School of Public Health, Department of Immunology and Infectious Disease, Boston, MA 02115, USA.);
Abstract	Previous work established that the principal sigma factor (RpoV) of virulent Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex, restores virulence to an attenuated strain containing a point mutation (Arg-515-->His) in the 4.2 domain of RpoV. We used the 4.2 domain of RpoV as bait in a yeast two-hybrid screen of an M. tuberculosis H37Rv library and identified a putative transcription factor, WhiB3, which selectively interacts with the 4.2 domain of RpoV in virulent strains but not with the mutated (Arg-515-->His) allele. Infection of mice and guinea pigs with a M. tuberculosis H37Rv whiB3 deletion mutant strain showed that whiB3 is not necessary for in vivo bacterial replication in either animal model. In contrast, an M. bovis whiB3 deletion mutant was completely attenuated for growth in guinea pigs. However, we found that immunocompetent mice infected with the M. tuberculosis H37Rv whiB3 mutant strain had significantly longer mean survival times as compared with mice challenged with wild-type M. tuberculosis. Remarkably, the bacterial organ burdens of both mutant and wild-type infected mice were identical during the acute and persistent phases of infection. Our results imply that M. tuberculosis replication per se is not a sufficient condition for virulence in vivo. They also indicate a different role for M. bovis and M. tuberculosis whiB3 genes in pathogenesis generated in different animal models. We propose that M. tuberculosis WhiB3 functions as a transcription factor regulating genes that influence the immune response of the host.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bacterial Proteins Metabolism DNA-Directed RNA Polymerases Mycobacterium Tuberculosis Growth & Development Sigma Factor Transcription Factors Amino Acid Sequence Animals Genetics Guinea Pigs Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Sequence Data Mutagenesis Mycobacterium Bovis Sequence Homology, Amino Acid Spleen Pathology Tuberculosis, Pulmonary Microbiology Mortality Two-Hybrid System Techniques Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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