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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.

Original publication

DOI

10.1099/mic.0.2007/014548-0

Type

Journal article

Journal

Microbiology

Publication Date

04/2008

Volume

154

Pages

1059 - 1067

Keywords

Animals, Antigens, Bacterial, Bacterial Proteins, Cattle, Female, Gene Deletion, Gene Expression Profiling, Genes, Regulator, Methyltransferases, Mice, Mutagenesis, Insertional, Mycobacterium bovis, Mycobacterium tuberculosis, Oligonucleotide Array Sequence Analysis, Tuberculosis, Tuberculosis, Bovine, Up-Regulation