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Lipid composition and transcriptional response of Mycobacterium tuberculosis grown under iron-limitation in continuous culture: identification of a novel wax ester

¹ TB Research group, Health Protection Agency, Centre for Emergency Preparedness and Response, Porton Down, Salisbury, Wiltshire SP4 0JG, UK
² School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
³ School of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK
⁴ Department of Pathology and Infectious Diseases, Royal Veterinary College, Royal College Street, London NW1 0TU, UK
⁵ Bacterial Microarray Group, Department of Cellular and Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK

Correspondence
Joanna Bacon
Joanna.bacon{at}hpa.org.uk

The low level of available iron in vivo is a major obstacle for microbial pathogens and is a stimulus for the expression of virulence genes. In this study, Mycobacterium tuberculosis H37Rv was grown aerobically in the presence of limited iron availability in chemostat culture to determine the physiological response of the organism to iron-limitation. A previously unidentified wax ester accumulated under iron-limited growth, and changes in the abundance of triacylglycerol and menaquinone were also observed between iron-replete and iron-limited chemostat cultures. DNA microarray analysis revealed differential expression of genes involved in glycerolipid metabolism and isoprenoid quinone biosynthesis, providing some insight into the underlying genetic changes that correlate with cell-wall lipid profiles of M. tuberculosis growing in an iron-limited environment.

Tables showing genes upregulated under iron-limitation, genes upregulated under iron-replete growth, and genes induced under iron-limitation in the chemostat and 24 h post-infection in the macrophage, are available as supplementary data with the online version of this paper.

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