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Microbiology 154 (2008), 1059-1067; DOI  10.1099/mic.0.2007/014548-0
© 2008 Society for General Microbiology

Characterization of two in vivo-expressed methyltransferases of the Mycobacterium tuberculosis complex: antigenicity and genetic regulation

Paul Golby1, Javier Nunez1, Paul J. Cockle1, Katie Ewer1, Karen Logan1,{dagger}, Philip Hogarth1, H. Martin Vordermeier1, Jason Hinds2, R. Glyn Hewinson1 and Stephen V. Gordon1,{ddagger}

1 Veterinary Laboratories Agency (Weybridge), New Haw, Addlestone, Surrey KT15 3NB, UK.
2 Bacterial Microarray Group, Department of Cellular and Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK

Correspondence
Stephen V. Gordon
stephen.gordon{at}ucd.ie

Genome sequencing of Mycobacterium tuberculosis complex members has accelerated the search for new disease-control tools. Antigen mining is one area that has benefited enormously from access to genome data. As part of an ongoing antigen mining programme, we screened genes that were previously identified by transcriptome analysis as upregulated in response to an in vitro acid shock for their in vivo expression profile and antigenicity. We show that the genes encoding two methyltransferases, Mb1438c/Rv1403c and Mb1440c/Rv1404c, were highly upregulated in a mouse model of infection, and were antigenic in M. bovis-infected cattle. As the genes encoding these antigens were highly upregulated in vivo, we sought to define their genetic regulation. A mutant was constructed that was deleted for their putative regulator, Mb1439/Rv1404; loss of the regulator led to increased expression of the flanking methyltransferases and a defined set of distal genes. This work has therefore generated both applied and fundamental outputs, with the description of novel mycobacterial antigens that can now be moved into field trials, but also with the description of a regulatory network that is responsive to both in vivo and in vitro stimuli.

Abbreviations: IFN-{gamma}, gamma-interferon; PPD, purified protein derivative (tuberculin); qRT-PCR, quantitative real-time polymerase chain reaction

{dagger}Present address: Emergent Biosolutions, 540–545 Eskdale Road, Winnersh Triangle, Wokingham, Berkshire RG41 5TU, UK.

{ddagger}Present address: School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin 4, Republic of Ireland.

The ArrayExpress (and BµG@Sbase) accession number for the microarray data in this paper is A-BUGS-59.

Two supplementary tables of primers are available with the online version of this paper.






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