Functional Genetic Diversity among Mycobacterium tuberculosis Complex Clinical Isolates: Delineation of Conserved Core and Lineage-Specific Transcriptomes during Intracellular Survival

Tuberculosis exerts a tremendous burden on global health, with approximately 9 million new infections and approximately 2 million deaths annually. The Mycobacterium tuberculosis complex (MTC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents...

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Vydáno v:PLoS pathogens Ročník 6; číslo 7; s. e1000988
Hlavní autoři: Homolka, Susanne, Niemann, Stefan, Russell, David G., Rohde, Kyle H.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 01.07.2010
Public Library of Science (PLoS)
Témata:
Gene expression
Gene Expression Profiling
Genetic aspects
Genetic diversity
Genetic Variation
Genetics and Genomics
Genetics and Genomics/Disease Models
Genetics and Genomics/Genetics of Disease
Genetics and Genomics/Microbial Evolution and Genomics
Genomics
Humans
Infections
Macrophages
Macrophages - microbiology
Microbiology
Microbiology/Medical Microbiology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Nucleic acids
Pathogenesis
Physiological aspects
Population
Proteins
RNA, Bacterial - analysis
Separation
Species Specificity
Studies
Tuberculosis
Tuberculosis - microbiology
United States
ISSN:1553-7374, 1553-7366, 1553-7374
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Shrnutí:Tuberculosis exerts a tremendous burden on global health, with approximately 9 million new infections and approximately 2 million deaths annually. The Mycobacterium tuberculosis complex (MTC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents of tuberculosis are more genetically and functionally diverse than appreciated previously. The impact of this natural variation on the virulence and clinical manifestations of the pathogen remains largely unknown. This report examines the effect of genetic diversity among MTC clinical isolates on global gene expression and survival within macrophages. We discovered lineage-specific transcription patterns in vitro and distinct intracellular growth profiles associated with specific responses to host-derived environmental cues. Strain comparisons also facilitated delineation of a core intracellular transcriptome, including genes with highly conserved regulation across the global panel of clinical isolates. This study affords new insights into the genetic information that M. tuberculosis has conserved under selective pressure during its long-term interactions with its human host.
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Conceived and designed the experiments: SH DGR KHR. Performed the experiments: SH KHR. Analyzed the data: SH SN DGR KHR. Wrote the paper: SH SN DGR KHR.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1000988