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          Institute: MPI für molekulare Genetik     Collection: Department of Computational Molecular Biology     Display Documents

ID: 404411.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
Mutation in the Transcriptional Regulator PhoP Contributes to Avirulence of Mycobacterium tuberculosis H37Ra Strain
Authors:Lee, Jong Seok; Krause, Roland; Schreiber, Jörg; Mollenkopf, Hans-Joachim; Kowall, Jane; Stein, Robert; Jeon, Bo-Young; Kwak, Jeong-Yeon; Song, Min-Kyong; Patron, Juan Pablo; Jorg, Sabine; Roh, Kyoungmin; Cho, Sang-Nae; Kaufmann, Stefan H.E.
Date of Publication (YYYY-MM-DD):2008-02-14
Title of Journal:Cell Host & Microbe
Issue / Number:2
Start Page:97
End Page:103
Copyright:© 2008 Elsevier Inc. All rights reserved.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Attenuated strains of mycobacteria can be exploited to determine genes essential for their pathogenesis and persistence. To this goal, we sequenced the genome of H37Ra, an attenuated variant of Mycobacterium tuberculosis H37Rv strain. Comparison with H37Rv revealed three unique coding region polymorphisms. One polymorphism was located in the DNA-binding domain of the transcriptional regulator PhoP, causing the protein's diminished DNA-binding capacity. Temporal gene expression profiles showed that several genes with reduced expression in H37Ra were also repressed in an H37Rv phoP knockout strain. At later time points, genes of the dormancy regulon, typically expressed in a state of nonreplicating persistence, were upregulated in H37Ra. Complementation of H37Ra with H37Rv phoP partially restored its persistence in a murine macrophage infection model. Our approach demonstrates the feasibility of identifying minute but distinct differences between isogenic strains and illustrates the consequences of single point mutations on the survival stratagem of M. tuberculosis.
Free Keywords:MICROBIO
Comment of the Author/Creator:Corresponding author:
Stefan H.E. Kaufmann
External Publication Status:published
Document Type:Article
Communicated by:Martin Vingron
Affiliations:MPI für Infektionsbiologie/Department of Immunology
MPI für Infektionsbiologie/Department of Cellular Microbiology
External Affiliations:1.Core Facility Protein Analysis, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany;
2.Core Facility Microarray, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany;
3.Department of Microbiology, Yonsei University, College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea.
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