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Mutation in the transcriptional regulator PhoP contributes to avirulence of Mycobacterium tuberculosis H37Ra strain.

Authors
 Jong Seok Lee  ;  Roland Krause  ;  Jorg Schreiber  ;  Hans-Joachim Mollenkopf  ;  Jane Kowall  ;  Robert Stein  ;  Bo-Young Jeon  ;  Jeong-Yeon Kwak  ;  Min-Kyong Song  ;  Juan Pablo Patron  ;  Sabine Jorg  ;  Kyoungmin Roh  ;  Sang-Nae Cho  ;  Stefan H.E. Kaufmann 
Citation
 Cell Host & Microbe, Vol.3(2) : 97-103, 2008 
Journal Title
 Cell Host & Microbe 
ISSN
 1931-3128 
Issue Date
2008
MeSH
Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics* ; Cells, Cultured ; Genetic Complementation Test ; Macrophages/microbiology ; Mice ; Molecular Sequence Data ; Mycobacterium tuberculosis/chemistry* ; Mycobacterium tuberculosis/pathogenicity* ; Point Mutation ; Polymorphism, Genetic ; Protein Structure, Tertiary/genetics ; Sequence Alignment ; Transcription Factors/chemistry ; Transcription Factors/genetics* ; Virulence
Keywords
Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics* ; Cells, Cultured ; Genetic Complementation Test ; Macrophages/microbiology ; Mice ; Molecular Sequence Data ; Mycobacterium tuberculosis/chemistry* ; Mycobacterium tuberculosis/pathogenicity* ; Point Mutation ; Polymorphism, Genetic ; Protein Structure, Tertiary/genetics ; Sequence Alignment ; Transcription Factors/chemistry ; Transcription Factors/genetics* ; Virulence
Abstract
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
Files in This Item:
T200803351.pdf Download
DOI
10.1016/j.chom.2008.01.002
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Immunology and Immunological Disease (면역질환연구소) > 1. Journal Papers
Yonsei Authors
Kwak, Jeong Yeon(곽정연)
Jeon, Bo Young(전보영)
Cho, Sang Nae(조상래)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108188
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