Functional genetic diversity among Mycobacterium tuberculosis complex clinical isolates: delineation of conserved core and lineage-specific transcriptomes during intracellular survival.

PLoS Pathogens
Susanne HomolkaKyle H Rohde

Abstract

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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Citations

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Datasets Mentioned

BETA
GPL5754
GSE21114

Methods Mentioned

BETA
genotyping
in vitro transcription
chip
PCR

Software Mentioned

SAS
JMP
Genespring
GraphPad Prism
Imagene

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