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Contrasting Transcriptional Responses of a Virulent and an Attenuated Strain of Mycobacterium tuberculosis Infecting Macrophages

Li, AH; Waddell, SJ; Hinds, J; Malloff, CA; Bains, M; Hancock, RE; Lam, WL; Butcher, PD; Stokes, RW (2010) Contrasting Transcriptional Responses of a Virulent and an Attenuated Strain of Mycobacterium tuberculosis Infecting Macrophages. PLOS ONE, 5 (6). e11066 (1)- e11066 (14). ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0011066
SGUL Authors: Butcher, Philip David Hinds, Jason Waddell, Simon John

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Abstract

Background: H37Rv and H37Ra are well-described laboratory strains of Mycobacterium tuberculosis derived from the same parental strain, H37, that show dramatically different pathogenic phenotypes. Methodology/Principal Findings: In this study, the transcriptomes of the two strains during axenic growth in broth and during intracellular growth within murine bone-marrow macrophages were compared by whole genome expression profiling. We identified and compared adaptations of either strain upon encountering an intracellular environment, and also contrasted the transcriptomes of the two strains while inside macrophages. In the former comparison, both strains induced genes that would facilitate intracellular survival including those involved in mycobactin synthesis and fatty acid metabolism. However, this response was stronger and more extensive for H37Rv than for H37Ra. This was manifested as the differential expression of a greater number of genes and an increased magnitude of expression for these genes in H37Rv. In comparing intracellular transcriptional signatures, fifty genes were found to be differentially expressed between the strains. Of these fifty, twelve were under control of the PhoPR regulon. Further differences between strains included genes whose products were members of the ESAT-6 family of proteins, or were associated with their secretion. Conclusions/Significance: Along with the recent identification of single nucleotide polymorphisms in H37Ra when compared to H37Rv, our demonstration of differential expression of PhoP-regulated and ESX-1 region-related genes during macrophage infection further highlights the significance of these genes in the attenuation of H37Ra.

Item Type: Article
Additional Information: Copyright: 2010 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, Cells, Cultured, Macrophages, Mice, Mycobacterium tuberculosis, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic, Virulence, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, MULTIDISCIPLINARY SCIENCES, GENOMIC ANALYSIS, GENE-EXPRESSION, BOVIS BCG, 2-COMPONENT SYSTEM, MURINE MACROPHAGES, ESCHERICHIA-COLI, HYPOXIC RESPONSE, TUBERCLE-BACILLI, INTERFERON-GAMMA, REGULATOR PHOP, General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLOS ONE
ISSN: 1932-6203
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Dates:
DateEvent
10 June 2010Published
Web of Science ID: WOS:000278599600022
URI: https://openaccess.sgul.ac.uk/id/eprint/107092
Publisher's version: https://doi.org/10.1371/journal.pone.0011066

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